Podcasts about tmb

BUFFALO, NY – August 15, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on August 13, 2025, titled “Clinical and analytical validation of MI Cancer Seek®, a companion diagnostic whole exome and whole transcriptome sequencing-based comprehensive molecular profiling assay.” In this study, first authors Valeriy Domenyuk and Kasey Benson, along with corresponding author David Spetzler from Caris Life Sciences in Irving, Texas, introduce MI Cancer Seek, an FDA-approved test designed to deliver comprehensive tumor profiling. MI Cancer Seek demonstrated strong concordance with other FDA-approved companion diagnostics and serves as a powerful tool to guide treatment decisions in both adult and pediatric cancer patients. Cancer remains one of the most complex and diverse diseases to treat. With many targeted therapies currently FDA-approved, selecting the right one for a specific patient requires detailed genetic insights. MI Cancer Seek addresses this need by analyzing both DNA and RNA from a single tumor sample. The tool identifies key biomarkers linked to FDA-approved treatments for several major cancers, including breast, lung, colon, melanoma, and endometrial cancers. One of the most significant strengths of MI Cancer Seek is its ability to deliver accurate and reliable results from minimal tissue input (50 ng). Even when analyzing formalin-fixed paraffin-embedded samples, which are widely used but often degraded, the test maintained high levels of accuracy. It successfully detected important genetic alterations such as PIK3CA, EGFR, BRAF, and KRAS/NRAS mutations and measured tumor mutational burden (TMB) and microsatellite instability (MSI), both of which are key indicators for immunotherapy response. In clinical comparisons, the test achieved over 97% agreement with other FDA-approved diagnostic tools, confirming its reliability in detecting critical biomarkers. Notably, it showed near-perfect accuracy in identifying MSI status in colorectal and endometrial cancers. The researchers also demonstrated that the test maintains precision across different lab conditions and varying DNA input levels, confirming its robustness for routine clinical use. Beyond its role as a companion diagnostic, MI Cancer Seek incorporates additional features developed under its predecessor, MI Tumor Seek Hybrid. These include detection of homologous recombination deficiency, structural variants, and cancer-related viruses. It also includes advanced tools such as the Genomic Probability Score for identifying the tissue of origin in cancers of unknown primary, as well as a gene signature to guide first-line chemotherapy in colorectal cancer. “One limitation to be considered is the low PPA for ERBB2 CNA detection.” By offering deeper genetic insights from a single, small sample, MI Cancer Seek has the potential to streamline diagnostics, reduce testing costs, and connect patients to effective therapies more quickly. As precision medicine continues to expand, this assay stands out as a comprehensive and efficient solution for meeting the evolving needs of modern oncology. DOI - https://doi.org/10.18632/oncotarget.28761 Correspondence to - David Spetzler - dspetzler@carisls.com Video short - https://www.youtube.com/watch?v=D4hd2FxCYY8 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

Today I'm joined by the incredible Steven McRae, Principal Dancer at The Royal Ballet, proud Aussie, devoted dad… and now, author! ______ DESCRIPTION LINKS Join the Balanced Ballerinas EXCLUSIVE Teachers Facebook Group here: https://www.facebook.com/groups/balancedballerinasteachers My Instagram! @thebalancedballerina Community Instagram! @balancedballerinas Facebook - Balanced Ballerinas And join the SECRET Facebook group here: https://www.facebook.com/groups/balancedballerinas/ Join the Balanced Ballerinas FREE 5 Day Challenge here: www.balancedballerinas.com/challenge Prenatal, healing or beginner ballet student? This course was designed for you: https://www.balancedballerinas.com/butterballet My Signature 12 Week Adult Ballet Course: https://www.balancedballerinas.com/12weekadultballetcourse The Marketing Blueprint For Dance Teachers & Studio Owners: https://www.balancedballerinas.com/TMB

This week on The OncoAlert Weekly Round Up, we spotlight precision oncology in action with top-tier studies making headlines:

Tonight on TMB, we'll have a long time friend of the program William Russell on the show. Bill as we know him has been a fixture in grass roots racing forever. He's a trackday guy, club racer, has raced nationals, crewed for riders doing the nationals, coached people etc.. I'm sure this will be a fun chat. Check him out on IG: @motofreak46Get signed up for your next TrackDaz event:http://trackdaz.trackrabbit.comYamaha OEM Oil Filter:https://amzn.to/3CBwpJqFire-Power Full Synth 10W-40https://amzn.to/4hVu23YThe above are Amazon affiliate links.. this means if you click to purchase, we make a commish at no additional cost to you. -thanks for your support **Want a deal on some boxo tools? Use the following link, and save 10% while also helping us get a bit of a commish! Its Win-Win!https://boxousa.com/TrackDazOr the code TrackDaz10**buy some celcuis drinks!https://amzn.to/3UVITBF**ROCKWELL WATCHES: Check out their website https://rockwelltime.com/Enter the code "TDZ20" at checkout and save 20% on a new Rockwell!!Sign up for your next TrackDaz event here: http://www.trackdaz.com*PIRELLI TIRES!! **You can get your Pirelli rubber from us directly on our registration site. Follow us on Facebook: / trackdaz Follow us on Instagram: @trackdazFollow the TrackDaz Crew:@chili144@jimmyz853@phen2210@gil823@formula_r@chili144@lgbrown_@dkm60@canea121@g_offsims@ricardo.abueg@trackdazkaren@fharo3@modbaez@m39023@dreek46@bubblesrides @r6_krissy_@shaunsummers62

A solo episode to conclude our Ballet Teaching series — discussing why great ballet teaching begins with who you are, how you grow, and the courage to keep evolving. _____ Join the Balanced Ballerinas EXCLUSIVE Teachers Facebook Group here: https://www.facebook.com/groups/balancedballerinasteachers My Instagram! @thebalancedballerina Community Instagram! @balancedballerinas Facebook - Balanced Ballerinas And join the SECRET Facebook group here: https://www.facebook.com/groups/balancedballerinas/ Join the Balanced Ballerinas FREE 5 Day Challenge here: www.balancedballerinas.com/challenge Prenatal, healing or beginner ballet student? This course was designed for you: https://www.balancedballerinas.com/butterballet My Signature 12 Week Adult Ballet Course: https://www.balancedballerinas.com/12weekadultballetcourse The Marketing Blueprint For Dance Teachers & Studio Owners: https://www.balancedballerinas.com/TMB

Continuing our mini-series The Art & Impact of Ballet Teaching, I'm joined by someone who has long inspired me with her grace, wisdom, and deep love of the art form—Jane Inglis-Keen. ___ Join the Balanced Ballerinas EXCLUSIVE Teachers Facebook Group here: https://www.facebook.com/groups/balancedballerinasteachers My Instagram! @thebalancedballerina Community Instagram! @balancedballerinas Facebook - Balanced Ballerinas And join the SECRET Facebook group here: https://www.facebook.com/groups/balancedballerinas/ Join the Balanced Ballerinas FREE 5 Day Challenge here: www.balancedballerinas.com/challenge Prenatal, healing or beginner ballet student? This course was designed for you: https://www.balancedballerinas.com/butterballet My Signature 12 Week Adult Ballet Course: https://www.balancedballerinas.com/12weekadultballetcourse The Marketing Blueprint For Dance Teachers & Studio Owners: https://www.balancedballerinas.com/TMB

In today's episode of Backpacker Radio, presented by The Trek, brought to you by Topo Athletic, we are joined by Jamie Lambert. We learn why Jamie doesn't have a trail name, and why it's definitely not Strap On, what it's like to thru-hike with your sister- which she did on the PCT in 2018, what it is about thru-hiking that makes it so addictive for her- having taken on long hikes every year over the last 8 seasons, what it's like to become social media famous, and much more. We wrap the show with an overview from day one of Trail Days, some new legislation that could result in finally completing the CDT, why a section of the PCT has been closed for MYLFs, our BS TED talks, and the triple crown of words we'll never pronounce correctly. Topo Athletic: Use code “TREKSPRING15” at topoathletic.com. Gossamer Gear: Use code “BACKPACKER20” for 20% off packs at gossamergear.com.  Ombraz: Use code “BACKPACKER30” for $30 off at ombraz.com/discount/backpacker30. Betterment: Learn more at betterment.com/trek. [divider] Interview with Jamie Lambert Jamie's Instagram Time stamps & Questions 00:05:00 - Trail Days Day 1 Recap 00:11:00 - Introducing Jamie 00:14:00 - How did you decide to hike the PCT with your sister? 00:18:45 - What's it like working for an orthodontist? 00:23:18 - What was it like to hike with your sister? 00:30:00 - Discussion about the Colorado Trail 00:35:08 - What is it about thru-hiking that you love? 00:37:45 - Have you hit a fork in the road feeling about thru-hiking? 00:41:10 - If you had to settle somewhere, where would you choose? 00:45:15 - What's the brief overview of the Tour du Mont Blanc? 00:47:15 - Why do people hike counter clockwise? 00:51:20 - Discussion about lodging and towns along the TMB 00:53:00 - Are there places along the trail where you could stay a few days? 00:55:10 - Discussion about guiding services on the TMB 00:56:51 - What time of year would you recommend? 01:00:30 - What changes in items did you carry? 01:01:45 - When did you know you wanted to hike the CDT too? 01:05:22 - Discussion about hiking the AT third 01:08:40 - How do you handle people fangirling around you? 01:11:02 - What's been the highlight of the AT for you so far? 01:12:05 - What's the most embarrassing thing that's happened to you while hiking? 01:14:05 - What's the scariest thing that's happened to you while hiking? 01:18:00 - Do you have any advice for solo female backpackers? 01:22:25 - What's your biggest beginner blunder? 01:24:44 - What do your resupplies look like these days? 01:30:00 - What shoes are you using? 01:33:30 - Peak Performance Question: What is your top performance enhancing or backpacking hack? 01:35:25 - Reminders: Take our survey! Listen to our episodes ad-free on Patreon and apply to blog for the Trek! Segments Trek Propaganda:  47 Years Later, the CDT Still Isn't Complete — New Legislation in Congress Aims To Change That by Katie Jackson This Section of the PCT Has Been Closed for 20 Years. The Reason? MYLFs by Kelsey Nannini QOTD:  If you had to give a TED Talk on something you're not a real expert on—but could fake it—what topic would you choose? Triple Crown of words you'll never pronounce correctly Mail Bag 5 Star Review [divider] Check out our sound guy @my_boy_pauly/ and his coffee. Sign up for the Trek's newsletter Leave us a voicemail! Subscribe to this podcast on iTunes (and please leave us a review)!  Find us on Spotify, Stitcher, and Google Play. Support us on Patreon to get bonus content. Advertise on Backpacker Radio Follow The Trek, Chaunce, Badger, and Trail Correspondents on Instagram. Follow Backpacker Radio, The Trek and Chaunce on YouTube. Follow Backpacker Radio on Tik Tok.  Our theme song is Walking Slow by Animal Years. A super big thank you to our Chuck Norris Award winner(s) from Patreon: Alex and Misty with NavigatorsCrafting, Alex Kindle, Andrew, Austen McDaniel, Brad & Blair Thirteen Adventures, Brent Stenberg, Bryan Alsop, Carl Houde, Christopher Marshburn, Coach from Marion Outdoors, Eric Casper, Erik Hofmann, Ethan Harwell, Gillian Daniels, Greg Knight, Greg Martin, Greg McDaniel may he bring honor to his name, Griffin Haywood, Hailey Buckingham, Lauren F, Patrick Cianciolo, Rebecca Brave, Sawyer Products, SPAM, Timothy Hahn, Tracy ‘Trigger' Fawns A big thank you to our Cinnamon Connection Champions from Patreon: Bells, Benjy Lowry, Bonnie Ackerman, Brett Vandiver, Chris Pyle, David, David Neal, Dcnerdlet, Emily Galusha, Greg Floravanti “Lumberjack”, Jack Greene, Jeanie, Jeanne Latshaw, Luke Netjes, Merle Watkins, Peter, Ruth S, and Spencer Hinson.

For episode 227 of our award-winning podcast⁠, we are celebrating our forty-third anniversary.On this date in 1982, we found ourselves kneeling at the altar in old St. Teresa's of Avila Catholic Church on West King Street in Carson City, Nevada. In the days since, we had a bunch of kids, saw the Information Age revolution, watched our country transform, and grew together as a couple. Sometime in there, we started our little publishing company Two Moore Books, LLC, and we published fifteen books.It's been a ride.As part of the TMB experience, we have writers from Nevada and across the country coming onto our little podcast. This schedule is tentative and (hello, redundancy) subject to change:June 8: Interview - Kendall BrownJune 11: Interview - Teresa Breeden (Nevada Author Network)June 15: Our regular podcastJune 18: Interview - Sue Dugan (Nevada Author Network)June 22: Interview - Rich MorenoJune 25: Suzanne Morgan (Nevada Author Network)June 29: Interview - Our regular podcastYou can meet and greet us at these two great book signings:-Barnes and Noble in south Reno on Saturday, June 28, 2025 at 1:00pm.-Artown at the Reno Public Market (Virginia and Plumb) on Saturday, July 5, 2025 at 1:00pm.Thank you for joining us on the big 43rd anniversary. TIA LYL!⁠please buy us coffee!⁠For those who listen on the way to work, we are on these fine podcast platforms: ⁠Spotify⁠ ⁠Apple⁠ ⁠Pocket Casts⁠ ⁠Radio Public⁠Note: Two Moore Books, LLC does not receive financial compensation for promoting third-party businesses and websites. We are speaking to our specific experiences. Your mileage may vary.

This week on The Balanced Ballerinas Podcast, I'm honoured to share a conversation with the legendary Lynne Charles as we launch our new mini-series, The Art & Impact of Ballet Teaching. Lynne's career is nothing short of extraordinary—dancing with American Ballet Theatre, London Festival Ballet, and as a principal with Hamburg Ballet and Deutsche Oper Ballet. But it's the teacher she's become that truly inspired this episode. _____ Join the Balanced Ballerinas EXCLUSIVE Teachers Facebook Group here: https://www.facebook.com/groups/balancedballerinasteachers My Instagram! @thebalancedballerina Community Instagram! @balancedballerinas Facebook - Balanced Ballerinas And join the SECRET Facebook group here: https://www.facebook.com/groups/balancedballerinas/ Join the Balanced Ballerinas FREE 5 Day Challenge here: www.balancedballerinas.com/challenge Prenatal, healing or beginner ballet student? This course was designed for you: https://www.balancedballerinas.com/butterballet My Signature 12 Week Adult Ballet Course: https://www.balancedballerinas.com/12weekadultballetcourse The Marketing Blueprint For Dance Teachers & Studio Owners: https://www.balancedballerinas.com/TMB

Los portavoces de los grupos con representación en el Parlamento de Bizkaia se sientan hoy ante los micrófonos de Radio Bilbao para debatir sobre algunos de los temas clave de la actualidad foral. Analizamos la sanción a la planta TMB de Arraiz por riesgos laborales, el avance del cable eléctrico entre Gatika y Burdeos, la nueva ordenanza de aparcamiento en Lekeitio tras la anulación judicial del decreto anterior, y la renuncia de la Diputación al proyecto del tren lanzadera entre Sestao y Areeta 

In this JCO Precision Oncology Article Insights episode, Jiasen He summarizes "Predictive Impact of Tumor Mutational Burden on Real-World Outcomes of First-Line Immune Checkpoint Inhibition in Metastatic Melanoma” by Dr. Miles C. Andrews, et al. published on June 07, 2024. Transcript The guest on this podcast episode has no disclosures to declare. Jiasen He: Hello and welcome to the JCO Precision Oncology Article Insights. I'm your host, Jiasen, and today we'll be discussing the JCO Precision Oncology article, "Predictive Impact of Tumor Mutational Burden on Real-World Outcomes of First-Line Immune Checkpoint Inhibition in Metastatic Melanoma," by Dr. Miles C. Andrews and colleagues. This study was supported by Foundation Medicine, a for-profit company that conducts FDA-regulated molecular diagnostics, including assays used to measure tumor mutational burdens, or TMB, as described in this article. Immune checkpoint inhibitor (ICI) therapy has become a cornerstone in the treatment of metastatic melanoma. They work by activating the patient's own immune system, representing a fundamentally different approach from traditional chemotherapy. Several biomarkers have emerged as promising tools to predict ICI therapy response, and TMB is one of the most extensively studied. TMB is defined as the number of somatic mutations per megabase of an interrogated genome sequence. In the KEYNOTE-158 study, patients with high TMB showed better response rates and longer progression-free survival compared to those with low TMB, which led to the FDA tumor-agnostic approval of TMB as a biomarker to guide ICI therapy. In this manuscript, Dr. Andrews and colleagues set out to answer an important question: does TMB predict outcomes of ICI therapy in real-world patients with advanced melanoma? To explore this, they analyzed de-identified data from the nationwide Flatiron Health-Foundation Medicine Clinico-Genomic Database (CGDB). To be included, patients needed to have had at least two visits to a Flatiron Health clinic and a Foundation Medicine Comprehensive Genomic Profiling report. Eligible patients had received first-line treatment with either monotherapy (nivolumab or pembrolizumab) or dual therapy with the combination of ipilimumab and nivolumab for metastatic melanoma. They also needed a tissue-based TMB score from either the FoundationOne or FoundationOne CDx genomic test. For this study, TMB less than 10 mutations per megabase was considered low TMB; TMB equal to or more than 10 mutations per megabase was considered high TMB; and TMB equal to or more than 20 mutations per megabase was considered very high TMB. Of the 497 patients in the final cohort, 29% had low TMB, while 71% had high TMB, and 50% had very high TMB. The authors observed that patients with very high TMB were more often male, had BRAF wild-type tumors, and were more likely to receive anti-PD-1 monotherapy. This group also had tumors more commonly sampled from brain and lung metastases. Patients with high TMB but not very high TMB were more likely to carry the BRAF V600K mutation and were least likely to have lung metastases. Meanwhile, those with low TMB tended to be younger and had disease limited to non-visceral sites. As expected, the presence of ultraviolet mutation signatures, a known driver of melanoma, was strongly associated with TMB. UV signatures were found in just 18% of the low TMB group, but in 89% of the high TMB and 93% of the very high TMB group. High TMB was found to be prognostic of improved real-world progression-free survival (PFS) and overall survival (OS) in patients receiving both monotherapy and dual immune checkpoint inhibitors, even after adjusting for other established prognostic factors. Interestingly, in the low TMB group, overall survival was likely confounded by the availability of effective second-line targeted therapy, particularly for BRAF-mutant patients. These patients had better outcomes compared to their BRAF wild-type counterparts, likely reflecting a greater reliance on salvage therapy in low TMB patients who derived less benefit from first-line immunotherapy. The authors then further examined the ICI outcomes using stepwise TMB thresholds, with TMB less than 10 as low, 10 to 19 as high, and equal to or more than 20 as very high. For those receiving ICI monotherapy, both PFS and OS were highest in the very high TMB group, followed by the high TMB group, and lowest in the low TMB group. However, in patients treated with dual ICI therapy, the results diverged. While low TMB patients still had the poorest outcomes, those with high TMB (mutations 10 to 19 per megabase) had better PFS and overall survival than those with very high TMB (mutations equal to or more than 20 per megabase). The authors then conducted exploratory multivariable modeling, showing that among very high TMB patients with BRAF mutations, dual ICI therapy was associated with a significantly higher hazard ratio compared to monotherapy. They concluded that dual ICI may not benefit, and could even harm, patients with very high TMB, whereas those with TMB between 10 and 20 mutations per megabase may get more from the intensified regimen. Importantly, as the authors stated in the manuscript, we need to note that in this cohort, very high TMB patients were more likely to have brain metastases at treatment initiation, be male, and lack BRAF V600E/K mutations—all factors associated with poorer prognosis. This might partially explain inferior outcomes to dual ICI in very high TMB patients, as patients were not randomly assigned to therapy in this retrospective, real-world study. As such, these findings should be interpreted with caution and validated in future studies. In summary, this study showed that in a real-world setting, high tumor mutational burden predicts better outcomes with immune checkpoint inhibitor therapy in patients with advanced melanoma. Interestingly, the authors found that dual ICI therapy may offer no added benefit for patients with very high TMB compared to ICI monotherapy. However, this was a retrospective, non-randomized study, and the cohorts were imbalanced for some known risk factors, which could confound outcomes. As a result, these findings should be interpreted with caution and will need to be validated in future prospective studies. Thank you for tuning into JCO Precision Oncology Article Insights. Don't forget to subscribe and join us next time as we explore more groundbreaking research shaping the future of oncology. Until then, stay informed and stay inspired. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

This week the TMB crew throw open the door and invite you all in as they discuss the viral vampire epic, Sinners (2025). They sink their teeth into this modern classic, headlined by the hip (Michael B Jordan)² and directed by the cool Coogler. Join in as they breakdown and banter about the blues, booze and blood in this blockbuster! 

On the TMB show, I have all sorts of personalities on. From Club to Pro, and just about everything between, I'm interested in talking to riders, team owners, crew members, etc.. This one is a club racer out of Minnesota. He races with the original CRA. I'm looking forward to sharing his stories and perspectives. Should be fun.Get signed up for your next TrackDaz event:http://trackdaz.trackrabbit.comYamaha OEM Oil Filter:https://amzn.to/3CBwpJqFire-Power Full Synth 10W-40https://amzn.to/4hVu23YThe above are Amazon affiliate links.. this means if you click to purchase, we make a commish at no additional cost to you. -thanks for your support **Want a deal on some boxo tools? Use the following link, and save 10% while also helping us get a bit of a commish! Its Win-Win!https://boxousa.com/TrackDazOr the code TrackDaz10**buy some celcuis drinks!https://amzn.to/3UVITBF**ROCKWELL WATCHES: Check out their website https://rockwelltime.com/Enter the code "TDZ20" at checkout and save 20% on a new Rockwell!!Sign up for your next TrackDaz event here: http://www.trackdaz.com*PIRELLI TIRES!! **You can get your Pirelli rubber from us directly on our registration site. Follow us on Facebook: / trackdaz Follow us on Instagram: @trackdazFollow the TrackDaz Crew:@chili144@jimmyz853@phen2210@gil823@formula_r@chili144@lgbrown_@dkm60@canea121@g_offsims@ricardo.abueg@trackdazkaren@fharo3@modbaez@m39023@dreek46@bubblesrides @r6_krissy_@shaunsummers62

In this episode expert guest Dr. CM Schade elaborates on the Texas Medical Board's revamped CME requirements for opioid prescriptions, which now focus only on direct patient care physicians. He offers insights into how the new rules bring flexibility while placing an emphasis on meticulous documentation. With decades of experience in legislative advocacy, Dr. Schade shares valuable tips on navigating these changes and encourages utilizing TMA's educational resources. Access the ondemand webinar - Prescribing and Monitoring of Controlled Substances Access current TMB rules

Learn more about Cindy's incredible work here: https://www.classfortheheart.com/ ____ Join the Balanced Ballerinas EXCLUSIVE Teachers Facebook Group here: https://www.facebook.com/groups/balancedballerinasteachers My Instagram! @thebalancedballerina Community Instagram! @balancedballerinas Facebook - Balanced Ballerinas And join the SECRET Facebook group here: https://www.facebook.com/groups/balancedballerinas/ Join the Balanced Ballerinas FREE 5 Day Challenge here: www.balancedballerinas.com/challenge Prenatal, healing or beginner ballet student? This course was designed for you: https://www.balancedballerinas.com/butterballet My Signature 12 Week Adult Ballet Course: https://www.balancedballerinas.com/12weekadultballetcourse The Marketing Blueprint For Dance Teachers & Studio Owners: https://www.balancedballerinas.com/TMB

You can find more of Dr Nya's important work at her website here: https://www.1nyama.com/ You can purchase 'Skin Colored Pointes' on Amazon here: https://www.amazon.com/Skin-Colored-Pointes-Interviews-Ballet/dp/1476687056 ________ Join the Balanced Ballerinas EXCLUSIVE Teachers Facebook Group here: https://www.facebook.com/groups/balancedballerinasteachers My Instagram! @thebalancedballerina Community Instagram! @balancedballerinas Facebook - Balanced Ballerinas And join the SECRET Facebook group here: https://www.facebook.com/groups/balancedballerinas/ Join the Balanced Ballerinas FREE 5 Day Challenge here: www.balancedballerinas.com/challenge Prenatal, healing or beginner ballet student? This course was designed for you: https://www.balancedballerinas.com/butterballet My Signature 12 Week Adult Ballet Course: https://www.balancedballerinas.com/12weekadultballetcourse The Marketing Blueprint For Dance Teachers & Studio Owners: https://www.balancedballerinas.com/TMB

Join the Balanced Ballerinas EXCLUSIVE Teachers Facebook Group here: https://www.facebook.com/groups/balancedballerinasteachers My Instagram! @thebalancedballerina Community Instagram! @balancedballerinas Facebook - Balanced Ballerinas And join the SECRET Facebook group here: https://www.facebook.com/groups/balancedballerinas/ Join the Balanced Ballerinas FREE 5 Day Challenge here: www.balancedballerinas.com/challenge Prenatal, healing or beginner ballet student? This course was designed for you: https://www.balancedballerinas.com/butterballet My Signature 12 Week Adult Ballet Course: https://www.balancedballerinas.com/12weekadultballetcourse The Marketing Blueprint For Dance Teachers & Studio Owners: https://www.balancedballerinas.com/TMB

Talkin' Motorbikes with Kevin "Kevdawg" Rodio, the team owner of Rodio Racing. This is the second time Kev has been on TMB. Since getting the Twins Cup Championship in MotoAmerica, what has he and his team been up to? What are the plans? Is Kevin moving the team over to Supersport class? What's the deal with the marketplace trolling?? Oh and most importantly Did they get the hummer fixed? -LOL Get signed up for your next TrackDaz event:http://trackdaz.trackrabbit.comYamaha OEM Oil Filter:https://amzn.to/3CBwpJqFire-Power Full Synth 10W-40https://amzn.to/4hVu23YThe above are Amazon affiliate links.. this means if you click to purchase, we make a commish at no additional cost to you. -thanks for your support **Want a deal on some boxo tools? Use the following link, and save 10% while also helping us get a bit of a commish! Its Win-Win!https://boxousa.com/TrackDazOr the code TrackDaz10**buy some celcuis drinks!https://amzn.to/3UVITBF**ROCKWELL WATCHES: Check out their website https://rockwelltime.com/Enter the code "TDZ20" at checkout and save 20% on a new Rockwell!!Sign up for your next TrackDaz event here: http://www.trackdaz.com*PIRELLI TIRES!! **You can get your Pirelli rubber from us directly on our registration site. Follow us on Facebook: / trackdaz Follow us on Instagram: @trackdazFollow the TrackDaz Crew:@chili144@jimmyz853@phen2210@gil823@formula_r@chili144@lgbrown_@dkm60@canea121@g_offsims@ricardo.abueg@trackdazkaren@fharo3@modbaez@m39023@dreek46@bubblesrides @r6_krissy_@shaunsummers62

Chris shares his eyepiece plans for the 7” TMB refractor and the guys continue the conversation on cleaning eyepieces. 

This one should be fun. a TMB epsiode with my longtime racing homie, Berto Wooldridge, to reminisce about our early days as Novices at Willow Springs and dive deep into his decades of experience in the club racing world. Berto has been a fixture in the AFM (American Federation of Motorcyclists) for years, even serving as president, and along the way, Trust me, this dude has stories!

JCO PO author Dr. David R. Gandara at UC Davis Comprehensive Cancer Center, shares insights into his JCO PO article, “Plasma Proteome–Based Test for First-Line Treatment Selection in Metastatic Non–Small Cell Lung Cancer,” one of the Top Articles of 2024. Host Dr. Rafeh Naqash and Dr. Gandara discuss how the PROphet® blood test supports first-line immunotherapy treatment decisions for metastatic NSCLC patients. TRANSCRIPT  Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations where we bring you engaging conversations with authors of clinically relevant and highly significant JCOPO articles. I'm your host, Dr. Rafeh Naqash, Podcast Editor for JCO Precision Oncology and Assistant Professor at the OU Health Stephenson Cancer Center at the University of Oklahoma.  Today, we are absolutely thrilled to be joined by Dr. David R. Gandara, Professor of Medicine Emeritus, Co-Director of the Center for Experimental Therapeutics and Cancer and Senior Advisor to the Director at UC Davis Comprehensive Cancer Center and also the senior author of the JCO Precision Oncology article entitled “Plasma Proteome–Based Test for First-Line Treatment Selection in Metastatic Non–Small Cell Lung Cancer.” This was one of the top performing articles of 2024, which is one of the reasons why we wanted to bring it in for a podcast discussion. At the time of this recording, our guest's disclosures will be linked in the transcript.  David, it is an absolute pleasure to have you today. For somebody like you who's led the field of lung cancer over the years, I'm really excited that you are going to be talking to us about this very interesting article, especially given that I think you're one of the big proponents of liquid biopsies and plasma-based testing. So, for the sake of our listeners - which comprises of academic oncologists, community oncologists, trainees - could you tell us where the biomarker landscape for non-small cell lung cancer is currently, and then we can try to take a deeper dive into this article. Dr. David Gandar: Okay. Well, thank you, Rafeh. It's a pleasure to be with you here today. And I think the current landscape for biomarkers for immunotherapy in non-small cell lung cancer is a mess. There's no better way to describe it. That makes this paper describing a new plasma proteomic assay even more important. So I'll just give you a perspective. There are 14 trials, phase three trials, that were done in first line non-small cell lung cancer advanced stage of immunotherapy versus chemotherapy and some other aspects, although they vary tremendously. Some of them were checkpoint monotherapy, some combined with chemotherapy, some combined with CTLA-4 inhibitors and so forth. 12 out of the 14 were positive, 12 got FDA approval. So there are 12 different options that an oncologist could use. Some of them were squamous cell only, some non-squamous, some used PD-L1 as a biomarker driven part of the study. Some used TMB, tumor mutational burden, some were agnostic. So when you put all of this together, an oncologist can pick and choose among all these various regimens. And by and large, it's PD-L1 that is the therapeutic decision maker.  ASCO actually, I think, has done the very best job of making a guideline, and it's, as you well know, called a living guideline, it's dynamic. And it is much easier to interpret, for me and I think for oncologists, than some of the other guidelines. It's got a green light and a red light, it may be kind of orange. And so the green light means this is a strong recommendation by the guideline committee. The orange means it's weak. For this purpose, non-small cell lung cancer, advanced stage, only a very few of the recommendations were green. It's mainly monotherapy and patients with cancers with a PD-L1 over 50%. In our surveys, at our meetings, less than 50% of oncologists in the United States are following these guidelines. Why? Because they don't trust the biomarker. And TMB has the same sort of limitations. They're not bad biomarkers, they're incomplete. They're only looking at a part of the story. So that means we need a new biomarker. And this is one that, I think, the data are quite impressive and we'll discuss it more. Dr. Rafeh Naqash: Absolutely. Like you said, abundance of many therapy options, but not necessarily everything works the same in different subsets of PD-L1 positivity or different subsets of patients with different levels of tumor burden. And like you said, again, difficulty in trying to identify the right biomarker. And that's a nice segue to this PROphet test that you guys ran. So can you tell us a little bit about the plasma proteomic assay? Because to the best of my knowledge, there's not a lot of validated plasma proteomic assays. A lot has been done on the tumor tissue side as far as biomarkers are concerned, but not much on the blood side, except for maybe ctDNA MRD testing. So what was the background for trying to develop a plasma-based proteomic test? And then how did this idea of testing it in the lung cancer setting come into play? And then we can go into the patient population specifics, the cohort that you guys have. Dr. David Gandara: Okay. Well, of course there's a company behind this assay, it's called OncoHost, and I'm a consultant for them. And they came to me two years ago and they said, “We have something different from anyone else.” And they explained the science to me, as well as some other lung cancer experts here in the United States. I'm not a proteomic expert, of course, but they developed an AI machine learning platform to assess plasma proteins in normal people and in people with cancer, and specifically then in people with non-small cell lung cancer. They identified over 7,000 proteins that had cancer implications for therapy, for resistance, for prognosis, etc., and they categorized them based on the literature, TCGA data, etc., and used this machine learning process to figure out which proteins might be most specific for non-small cell lung cancer. And that's where they started. And so out of that 7,000 proteins, where they've identified which ones are angiogenic, which ones are involved with EMT or cell cycle or whatever it might be, they distilled it down to 388 proteins which they thought were worth testing in non-small cell lung cancer. And that's when I became involved.  They had a retrospective cohort of patients that had been treated with various immunotherapies. They looked at the analytic validation first, then applied it to this cohort. It looked good. Then they had a very large cohort, which they split, as you usually do with an assay, into a test set and then a validation set. For the test set, they wanted something more than a response. They wanted some indicator of long term benefit because that's where immunotherapy differentiates itself from chemotherapy and even targeted therapy. And so they picked PFS at 12 months. And I became involved at that point and it looked really good. I mean, if you look at the figures in the manuscript, the AUC is superb about their prediction and then what actually happened in the patient. And then in this paper, we applied it to a validation set of over 500 patients in a prospective trial, not randomized, it's called an observational trial. The investigator got to pick what they thought was the best therapy for that patient. And then in a blinded fashion, the proteomic assay experts did the analysis and applied it to the group.  And so what that means is some of the patients got chemotherapy alone, some got checkpoint immunotherapy monotherapy, some got in combination with chemotherapy. None of the patients in this study got a CTLA-4 inhibitor. That work is ongoing now. But what the study showed was that this assay can be used together with PD-L1 as what I would call a composite biomarker. You take the two together and it informs the oncologist about the meaning of that PD-L1. I'll give you an example. If that patient has a PD-L1 over 50% in their cancer and yet the PROphet test is negative, meaning less than 5 - it's a 0 to 10 scale - that patient for survival is better served by getting chemotherapy and immunotherapy. However, if the PROphet test is positive and the PD-L1 is over 50%, then the survival curves really look equivalent. As I said earlier, even in that group of patients, a lot of oncologists are reluctant to give them monotherapy. So if you have a test and the same sort of example is true for PD-L1 0, that you can differentiate. So this can really help inform the oncologist about what direction to go. And of course then you use your clinical judgment, you look at what you think of as the aggressiveness of the tumor or their liver metastases, etc. So again, that's how this test is being used for non-small cell lung cancer. And maybe I'll stop there and then I'll come back and add some other points. Dr. Rafeh Naqash: I definitely like your analogy of this therapy de-escalation strategy. Like you mentioned for PD-L1 high where the PROphet test is negative, then perhaps you could just go with immunotherapy alone. In fact, interestingly enough, I was invited to a talk at SITC a couple of weeks back and this exact figure that you're referring to was one of the figures in my slide deck. And it happened by chance that I realized that we were doing a podcast on the same paper today.  So I guess from a provocative question standpoint, when you look at the PD-L1 high cohort in the subset where you didn't see a survival difference for chemo plus immunotherapy versus immunotherapy alone, do you think any element of that could have been influenced by the degree of PD-L1 positivity above 50%? Meaning could there have been a cohort that is, let's say PD-L1 75 and above, and that kind of skews the data because I know you've published on this yourself also where the higher the PD-L1 above 50%, like 90% PD-L1 positivity survival curves are much better than 50% to 89%. So could that have somehow played a role? Dr. David Gandara: The first thing to say is that PD-L1 and the PROphet score, there's very little overlap. I know that sounds surprising, but it's also true for tumor mutational burden. There's very little overlap. They're measuring different things. The PD-L1 is measuring a specific regulatory protein that is applicable to some patients, but not all. That's why even in almost all of the studies, people with PD-L1 0 could still have some survival benefit. But in this case they're independent. And not in this paper, but in other work done by this group, the PROphet group, they've shown that the PROphet score does not seem to correlate with super high PD-L1. So it's not like the cemiplimab data where if you have a PD-L1 of greater than 90%, then of course the patient does spectacularly with monotherapy. The other thing that's important here is they had a group of around a little less than 100 patients that got chemotherapy alone. The PROphet score is agnostic to chemotherapy. And so that means that you're not just looking at some prognostic factor. It's actually clinical utility on a predictive basis. Dr. Rafeh Naqash: I think those are very important points. I was on a podcast a couple of days back. I think there's a theme these days we're trying to do for JCO Precision Oncology, we're trying to do a few biomarker based podcasts, and the most recent one that we did was using a tissue transcriptome with ctDNA MRD and you mentioned the composite of the PD-L1 and the PROphet test and they use a composite of the tissue transcriptome. I believe they called it the VIGex test as well as MRD ctDNA. And when your ctDNA was negative at, I believe, the three month mark, those individuals had the highest inflamed VIGex test or highest infiltration of T cells, STING pathway, etc. So are there any thoughts of trying to add or correlate tissue based biomarkers or ctDNA based correlations as a further validation in this research with the company? Dr. David Gandara: Right. So there are many things that are being looked at, various composites looking at the commutations that might affect the efficacy of immunotherapy and how they correlate with profit positivity or negativity. And I'll just give the examples of STK11 and KEAP1. As you know, there's some controversy about whether these are for immunotherapy, whether they're more prognostic or predictive. I'm one of the co-authors among many in the recently published Nature paper by Dr. Skoulidis and the group at MD Anderson which report that for KEAP1 positive especially, but also SDK11 mutated getting immunotherapy, that that's where the CTLA-4 inhibitors actually play the greatest role. So realizing that this is still controversial, there are preliminary data, not published yet, that'll be presented at an upcoming meeting, looking at many of these other aspects, P53, SCK11, KEAP1, other aspects, TMB, that's actually already published, I think in one of their papers. So yes, there's lots of opportunities.  The other cool thing is that this isn't a test, it's a platform. And so that means that the OncoHost scientists have already said, “What if we look at this test, the assay in a group of patients with small cell lung cancer?” And so I just presented this as a poster at the world conference in San Diego. And it turns out if you look at the biology of small cell, where neither PD-L1 nor TMB seem to be very important, if you look at the biology of small cell and you form an assay, it only shares 44 proteins out of the 388 with non-small cell. It's a different biology. And when we applied that to a group of patients with small cell lung cancer, again it had really pretty impressive results, although still a fairly small number of patients. So we have a big phase three study that we're doing with a pharmaceutical company developing immunotherapy where we are prospectively placing the PROphet test in a small cell trial.  The platform can also be altered for other cancer types. And at AACR, Dr. Jarushka Naidoo presented really impressive data that you can modify the proteins and you can predict immunotherapy side effects. So this is not like a company that says, “We have one test that's great for everything.” You know how some companies say, “Our test, you can use it for everything.” This company is saying we can alter the protein structures using AI machine learning assisted process to do it and we can have a very informed assay in different tumor types and different situations. So to me, it's really exciting. Dr. Rafeh Naqash: Definitely to me, I think, combining the AI machine learning aspect with the possibility of finding or trying to find a composite biomarker using less invasive approaches such as plasma or blood, definitely checks a lot of boxes. And as you mentioned, trying to get it to prospective trials as an integral biomarker perhaps would be likely the next step. And hopefully we see some interesting, exciting results where we can try to match or stratify patients into optimal combination therapies based on this test.  So now to the next aspect of this discussion, David, which I'm really excited about. You've been a leader and a mentor to many. You've led ISLC and several other corporate group organizations, et cetera. Can you tell us, for the sake of all the listeners, junior investigators, trainees, what being a mentor has meant for you? How your career has started many years back and how it's evolved? And what are some of the things that you want to tell people for a successful and a more exciting career as you've led over the years? Dr. David Gandara: Well, thank you for the question. Mentoring is a very important part of my own career. I didn't have an institutional mentor when I was a junior investigator, but I had a lot of senior collaborators, very famous people that kind of took me under their wing and guided me. And I thought when I basically establish myself, I want to give back by being a mentor to other people. And you wouldn't believe the number of people that I'm even mentoring today. And some of them are not medical oncologists, they're surgeons, they're radiation oncologists, they're basic scientists. Because you don't have to be an expert in that person's field to be a mentor. It helps, but in other words, you can guide somebody in what are the decision making processes in your career. When is it time to move from this institution onward because you can't grow in the institution you're in, either because it's too big or it's too small? So I established a leadership academy in the Southwest Oncology Group, SWOG. I've led many mentoring courses, for instance, for ISLC, now for International Society Liquid Biopsy, where I'm the executive committee liaison for what's called The Young Committee. So ISLB Society, totally devoted to liquid biopsy, six years old now, we have a Young Committee that has a budget. They develop projects, they publish articles on their own, they do podcasts. So what I'm saying is those are all things that I think opens up opportunities. They're not waiting behind senior people, they are leading themselves.  We just, at our International Lung Cancer Congress, reestablished a fellows program where a group of fellows are invited to that Huntington beach meeting. It's now in its 25th year and we spend a day and a half with them, mentoring them on career building. I'll just give you my first, I have the “Letterman Top 10”. So my first recommendation is if all you have is lemons, make lemonade. And what I'm meaning is find what you can do at your institution if you're a junior person, what you can claim to be your own and make the very best of it. But then as you get further along in my recommendations, one of them is learn when to say ‘no'. Because as a junior investigator the biggest threat to your career is saying ‘yes' to everybody and then you become overwhelmed and you can't concentrate. So I'll stop there. But anyway, yes, mentoring is a big part of my life. Dr. Rafeh Naqash: Well, thank you, David. This is definitely something that I'm going to try to apply to my career as well. And this has been an absolute pleasure, especially with all the insights that you provided, not just on the scientific side but also on the personal career side and the mentorship side. And hopefully we'll see more of this work that you and other investigators have led and collaborated on. perhaps more interesting plasma based biomarkers. And hopefully some of that work will find its home in JCO Precision Oncology. Thank you again for joining us today. Dr. David Gandara: My pleasure. Dr. Rafeh Naqash: And thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcasts.   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service organization, activity or therapy should not be construed as an ASCO endorsement.   Dr. David Gandara Disclosures: Consulting or Advisory Role Company: Henlius USA, Foundation Medicine, Janssen Pharma, Merck & Co, Mirati Therapeutics, Regeneron, AstraZeneca, Guardant Health, Genentech, Exact Sciences  Research Funding Company: Amgen, Genentech, Astex Pharma  

Chris shares his first light report with the 7” TMB refractor. Shane joined Chris for second light with the 7” and the guys talk about the views. 

JCO PO authors Dr. Philippe Bedard (Staff Medical Oncologist at Princess Margaret Cancer Centre and Professor of Medicine at University of Toronto) and Dr. Alberto Hernando Calvo (Medical Oncologist at Vall d´Hebron University Hospital) share insights into their JCO PO article, “Combined Transcriptome and Circulating Tumor DNA Longitudinal Biomarker Analysis Associates With Clinical Outcomes in Advanced Solid Tumors Treated With Pembrolizumab,” one of the top downloaded articles of 2024. Host Dr. Rafeh Naqash and Drs. Bedard and Hernando Calvo discuss how combined transcriptome and ctDNA longitudinal analysis associates with pembrolizumab outcomes. TRANSCRIPT Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Rafeh Naqash, podcast editor for JCO Precision Oncology and Assistant Professor at the OU Health Stephenson Cancer Center at the University of Oklahoma.  Today we are excited to be joined by Dr. Philippe Bedard, Staff Medical Oncologist at the Princess Margaret Cancer Center and Professor of Medicine at the University of Toronto, as well as by Dr. Alberto Hernando-Calvo, Medical Oncologist at the Vall d'Hebron University Hospital, both authors of the JCO Precision Oncology article titled, “Combined Transcriptome and Circulating Tumor DNA Longitudinal Biomarker Analysis Associates With Clinical Outcomes in Advanced Solid Tumors Treated With Pembrolizumab.”  Thank you for joining us today. Phil and Alberto. Dr. Alberto Hernando-Calvo: Thank you. Dr. Philippe Bedard: Great to be with you. Thanks for having us.  Dr. Rafeh Naqash: One of the reasons we do this podcast, as some of the listeners who listen to this podcast regularly may know, is to bring in novel approaches and try to understand how the field is moving towards a space where we are understanding biomarkers better. So your manuscript that was published in JCO Precision Oncology fulfills many of those criteria. And interestingly enough, I was at a conference at the Society for Immunotherapy of Cancer last month earlier in November and a lot of excitement at SITC was revolving around novel transcriptomic biomarkers, proteomic biomarkers or imaging based biomarkers. So could you tell us a little bit about why you started looking at biomarkers? This is an extremely competitive field. Why did you think that looking at the transcriptome is somewhat different from or more interesting from tumor mutational burden PDL-1 than other biomarkers that we currently use? And that question is for you Alberto to start off.  Dr. Alberto Hernando-Calvo: So I think gene expression profiles may have a predictive performance as compared to already existing biomarkers and this was one of the points that we describe in our manuscript. The gene expression signature that we developed back in 2019 at Vall d'Hebron Institute of Oncology was initially developed based on over 45 different tumor types and tested in over 1000 patients treated with antiPD-1 and anti PDL-1. And back then and in this manuscript, we proved that for instance the gene expression signature VIGex that we developed has a potential complementary role to other predictive biomarkers. In this case, we observe this predictive power with ctDNA dynamics and we then see a correlation with other existing biomarkers such as tumor mutational burden. So I don't think we need to use one or the other, but rather they may have additive predictive power. So we need to better individualize predictive biomarkers based on tumor types and select the best combination possible to improve the performance.  Dr. Rafeh Naqash: I completely agree that one size does not fit all, especially in the landscape of immunotherapy. From your perspective, when you developed the original signature, how did you choose what genes to look at? I looked at the manuscript, on the methodology side, some of the signatures are pro-inflammatory STING interferon gamma based, so how did you try to identify that these are the 7 to 10 or whatever number of signatures on the transcriptome side? And then why did you try to combine it with ctDNA based changes?  Dr. Alberto Hernando-Calvo: Back in our initial manuscript, published in Med from Cell Press, we developed the VIGex gene expression signature, as I mentioned, with taking into consideration over 1000 tumor samples from FFPE that we can consider real world samples because they are from real patients coming from the clinic notes as part of real investigational protocol doing or performing biopsies on patients. We did observe after doing a VIGex research and doing different tests, we eventually collected these 12 different genes. Because there is a combination of both genes involved in the interferon gamma pathway, we have genes associated with Tregs as well as T cell memory cells. So it's not only looking at genes that are associated with T cell activation or CD8+ T cell infiltration, but also looking at genes that may be overactivated, overexpressed, an immunosuppressive tumor microenvironment. So it was both selecting genes, the minimum number of genes to do it more scalable and having the minimum dataset of genes and including in the signature genes that are already at targets for immune sequent inhibitors or are being tested in immunotherapy combinations.  Dr. Rafeh Naqash: Thank you. And Phil, for the sake of our listeners, could you elaborate upon this aspect of using ctDNA? So this was tumor-informed ctDNA from what I understood in the manuscript. You guys basically try to use it to understand changes in the ctDNA with treatment and then try to combine it with the transcriptome signature. How did the idea come up initially and how did you plan on combining this with an RNA-based signature? Because I have seen manuscripts and other data where people are either using one or the other, but not necessarily both together. So how did you guys come up with that idea? Dr. Philippe Bedard: Well, we thought that this was a great opportunity to look at the combination of the transcriptome as well as the ctDNA dynamics because we had run an investigator-initiated phase 2 clinical trial called INSPIRE at our institution at Princess Margaret from 2016 to 2018, where patients across five different tumor groups received single agent pembrolizumab. And we really did a deep dive on these patients where there were tumor biopsies before and while on treatment. We did exome sequencing, we did RNA sequencing to capture the transcriptome. And in a prior analysis, we had partnered with Natera to look at their Signatera assay, which is a bespoke ctDNA assay, to look at ctDNA dynamics using this test and the association with response outcomes as well as survival outcomes. So we thought that this was a really unique data set to try and address the question of whether or not there was complementarity in terms of looking at the transcriptome and transcriptome signatures of IO benefit together with the ctDNA dynamics. Dr. Rafeh Naqash: From a patient treatment standpoint, it sounded like you mostly tried to include individuals who were treated with pembrolizumab. Did this not include individuals who were treated with chemoimmunotherapy or chemotherapy with pembrolizumab? Just pembrolizumab alone? And if that's the case, some of the tumor types there included, from what I remember, ovarian cancer and some other unusual cancers that don't necessarily have approvals for single agent pembrolizumab, but perhaps in the TMB-high setting. So can you elaborate on the patient selection there for the study?  Dr. Philippe Bedard: Yeah, that's a great question. So at the time that the study was designed in 2015, this was really the early days of immune checkpoint inhibitor therapy, so we didn't have the approvals that we have now in specific tumor types for immunotherapy and chemotherapy combinations. So when the study was designed as an investigator initiated clinical trial, the idea was really to capture patients across different tumor types - so head and neck squamous cell carcinoma, malignant melanoma, ovarian cancer, triple negative breast cancer, and a kind of mixed histology solid tumor cohort, where we knew that there were some patients who were going to be immunotherapy responsive, where there was already approvals or evidence of single agent activity, and others where the responses were more anecdotal, to try and understand in a phase 2 clinical trial with kind of a deep dive, which patients benefited from treatment and which didn't. Dr. Rafeh Naqash: Interesting approach. Going to the results, Alberto, could you help us understand some of the important findings from these data? Because there's different sections of how you tried to look at the response rates, the survival, looking at the immune deconvolution, if you could explain that. Dr. Alberto Hernando-Calvo: So the first thing that we tried was to further confirm the external validation of this immune gene expression signature, VIGex in the INSPIRE asset. So what we observed at VIGex-Hot, the category defined by VIGex-Hot tumor microenvironment, was associated with better progression free survival. After including that in a multivariable analysis adjusted by other biomarkers such as TMB, PDL-1 or tumor type, this was also confirmed for overall survival. So then the next step was to really try to hypothesize if the addition of ctDNA dynamics, taking into consideration the ctDNA quantification at baseline as compared to cycle three, if those dynamics could further improve the predictive performance of VIGex categories taken in the baseline samples. What we did observe was that, for instance, VIGex-Hot tumors in baseline tumor samples that were having a ctDNA decrease, as I mentioned before on cycle three assessment as compared to baseline, were having both better progression free survival and better prognosis overall. Another important finding was the evaluation of response rate across tumor types considering both biomarkers. I would say the most important finding is that when we were considering a cold tumor microenvironment in baseline samples before pembrolizumab initiation plus an increase in ctDNA values, what we observed is that those patients were having a 0% response rate. So this may help as a future strategy either for intensification of immunotherapy regimens in a more individualized way or for an early stop to immunotherapy and try to avoid financial toxicities as well as toxicities for our patients. Dr. Rafeh Naqash: From the data that you showed, it seems that there was a strong correlation, as you sort of mentioned, between individuals that had ctDNA clearance and baseline immune pro-inflammatory signatures. So do you really need the transcriptome signature or could the ctDNA just serve as an easy quick surrogate? Because from a cost standpoint, doing whole transcriptome sequencing or more RNA sequencing or tissue standpoint, where tissue is often limited, can become a big issue. So do you think that validation of this may perhaps more revolve around using ctDNA as an easier metric or surrogate? Or am I overestimating the utility of ctDNA? Dr. Philippe Bedard: I think it's a really good question. In our data set which was relatively small, there were 10 patients who had ctDNA clearance, meaning ctDNA that was positive at baseline was not detected. And so 9 out of those 10 patients, as you alluded to, were VIGex-Hot. So the question is a good one, could you do the same with just ctDNA clearance alone, particularly in identifying these patients who really do well, who have long term disease control on immunotherapy? I think it's a tough question to answer because the field is also changing in terms of sensitivity of detection of ctDNA tests. So we know now that there are newer generations of tests which can detect even at logs down in terms of allele variants in the circulation. So I think we need more data to address the question. I think it is important as to what is the best test, what is the endpoint that we should be using from a drug development point of view in terms of really trying to push and understand which treatment regimens are the most effective and have early readouts in terms of activity. Because we all recognize in the clinic that radiographic response doesn't tell the whole story, especially early radiographic assessments using RECIST or other criteria that we apply in clinical trials. Dr. Rafeh Naqash: From a clinical trial standpoint, we often talk about validation of these studies. You may have heard of other tests where, for example, the NCI iMatch, which is incorporating transcriptome sequencing based approach to stratify patients as an integral biomarker for treatment stratification. Is that something that you guys are thinking of using, this approach where individuals who are signature highly inflamed perhaps get lesser therapies or there's a de-intensification of some sort similar to what people are trying to do with ctDNA-based approaches? Dr. Philippe Bedard: I think that's a great question. I think it makes a lot of sense. And certainly, with the new wave antibody drug conjugates in terms of identifying patients who have expression of targets for antibody drug conjugates, that's very attractive as an approach because we don't necessarily have IHC markers for all of the different targets of antibody drug conjugates. We don't necessarily have IHC markers to completely understand different contributions to the tumor microenvironment and whether or not tumors are inflamed. But it's also a challenging approach too because RNA-seq currently is not a routine clinical test. Sometimes there are issues, particularly in patients who have stored specimens that are formalin-fixed and paraffin-embedded in terms of the quality of the RNA for RNA sequencing. And it's not always feasible to get pre-treatment biopsies and turn them around in an approach. So I think it is an attractive approach for clinical trials, but it's a hypothesis that needs to be tested. It's not something that is ready for clinical prime time today in 2024. Dr. Rafeh Naqash: One of the other interesting observations that I came across in your manuscript was that tumor mutational burden, interestingly, did not correlate with signature high tumors. What is the explanation for that? Because generally you would expect a TMB high to perhaps also have an immune gene high signature. Could it have something to do with the tumor types because there was a heterogeneous mixture of tumor type? Or I'm not sure. What else could you possibly think of that you didn't see those correlations or just sample size limitations? Dr. Alberto Hernando-Calvo: Yes. So our findings are consistent with prior data suggesting for instance T cell inflamed gene expression profile was also not correlated with tumor mutational burden and both biomarkers in a prior publication. So to have additive predictive performance for identifying patients most likely to benefit from anti PD-1 regimen, so we somehow were expecting this observation, the fact that both biomarkers are not very correlated. Dr. Rafeh Naqash: So given the proof of concept findings from your study, Phil, what is the next interesting step that you guys are thinking of to expand this? Would you think that a nivolumab-ipilimumab treated cohort would have similar findings? Or is this a treatment specific single agent immunotherapy specific correlation that you found versus something else that you may find in a nivo-ipi cohort or a doublet immune checkpoint cohort?  Dr. Philippe Bedard: The findings are really hypothesis generating. They require additional validation. And you're quite right, there may be nuances in terms of specific tumor types, combinations with other immunotherapy or combinations with chemotherapy or other agents. So I think it would be great if there are other data sets that are collecting this type of information that have ctDNA dynamics and also have transcriptome and potentially exome or genome analysis to look at these types of questions because the field is moving quickly and we really need more data sets in order to understand some of the nuances and greater numbers to validate the signals that we see. Dr. Rafeh Naqash: And one thing, as you said, the field is definitely moving very quickly. I was meeting with a company an hour back and they have an imaging-based approach using fresh tissue to look at pharmacodynamic biomarkers. And I used to work in the NCI with a group that was very interested and they developed an immuno-oncology pharmacodynamic panel that has been used and published in a few clinical trials where they did phosphorylation status. So the final theme that comes out of most of these research based studies that are being done is that one size does not fit all. But the question that comes to my mind is how many things do you necessarily need to combine to get to a predictive biomarker that is useful, that is patient centric, and that perhaps is able to identify the right therapy for the right patient. What is your take on that, Phil?  Dr. Philippe Bedard: Yeah, that's a great question too. The challenge is it depends on the context in terms of what degree of positive predictive value do you need as well as the negative predictive value to drive clinical decisions. So I think in certain situations where you don't have other approved treatment options and with a therapy that is potentially low toxicity and low financial toxicity, then I think the bar is very high in terms of being able to really confidently identify that patients aren't going to benefit. I think the nuance and the challenge becomes when you move into earlier lines of therapy, or when you talk about combinations of agents, or trying to understand within the context of other available options, particularly with treatments that have significant side effect profiles as well as financial risks, then it becomes a much more nuanced question and you really need comparative studies to understand how it fits versus the existing treatment paradigm. So I'm not really answering your question with a specific number because I think it's hard to give you a number. Some of that we also need input from patients in terms of what kind of level of validation do you need and what kind of level of discrimination do you need in order to drive decisions that are meaningful for them. Dr. Rafeh Naqash: Definitely early days, as you pointed out. More and more work in this field will hopefully lead us in the direction that we all want to go in.  Now, going to a different aspect of this podcast, which is trying to understand the trajectories for both of you, Phil and Alberto. And as you mentioned, this project seemed to have started in 2015. So I'm guessing there's a history there between Princess Margaret and Vall d'Hebron. Could you highlight that a little bit? And then perhaps, Alberto, after that you could tell us a little bit about your career when you worked at Princess Margaret as a fellow and then now back at Vall d'Hebron. Phil, you as well. Dr. Philippe Bedard: So absolutely. We have a long history of collaborating with Vall d'Hebron in Barcelona. It's really a great cancer institution with a lot of like minded individuals. We have a formal partnership and we have a lot of informal links in terms of scientists and clinicians who we work with and who we collaborate with on early phase clinical trials, as well as through different investigator networks and other translational projects. So this was really how this collaboration came about and we were fortunate to have Alberto, who came to work with us for two years and brought this great idea of looking at this signature they had developed at Vall d'Hebron in their phase one group and applying it to a data set that we had through the INSPIRE clinical trial.  Dr. Rafeh Naqash: Sounds like a very successful academia-academic collaboration, which is very nice to see. So, Alberto, could you tell us a little bit about your career trajectory and how you ended up at Princess Margaret and then back at Vall d'Hebron and what you do currently? Dr. Alberto Hernando-Calvo: Yes. So I did my oncology residency at Vall d'Hebron in Barcelona, Spain. Then I decided to further specialize in early drug development as well as head and neck cancer oncology. So I decided to pursue a clinical research fellowship under the supervision of Phil Bedard, among others. And so we decided to further validate the signature that we had developed both in the cancer genomic lab at Vall d'Hebron Institute of Oncology and the phase one unit at Vall d'Hebron, and apply the signature that have been originally tested in patients receiving anti PD-1 or anti PDL-1 combinations in early phase clinical trials. In the phase 2 clinical trial of INSPIRE, where we also had ctDNA dynamics and allowed us to test both biomarkers and see that additive predictive power when we were using both. That was one of my research topics under the mentorship of Dr. Bedard and my fellowship at Princess Margaret. And this was one of the manuscripts describing all the findings of this collaboration between Vall d'Hebron and Princess Margaret Cancer Center. Dr. Rafeh Naqash: And then, Phil, if you could highlight some of the things that you've done over the course of your career and perhaps some advice for early career junior investigators and trainees.  Dr. Philippe Bedard: I finished my oncology, medical oncology training at the University of Toronto in 2008. And then I did a breast cancer fellowship in Brussels at Breast International Group. At the time, I was really intrigued because it was really kind of the early days of microarray and RNA signatures in terms of expressing signatures were being used as part of a clinical trial that BIG was running called the MINDACT Study. And so when I finished my fellowship, I came back to Princess Margaret, started on staff. I've been here now for 15 years. I was fortunate to work with the phase 1 group and kind of my career has sort of morphed in terms of early drug development as well as genomics. I've been involved with the American Association for Cancer Research project GENIE, where I'm the current chair. This is really an international data sharing project with panel based sequencing, which both Princess Margaret and Vall d'Hebron have contributed to. And I've been fortunate to work with a number of really talented early career investigators like Alberto, who spend time with us in our drug development program and launched transitional research projects that leverage some existing data sets at their own institutions and also bring together with different research groups at our institution to lead to publications like this one. Dr. Rafeh Naqash: Thank you so much. This was very exciting. Phil and Albert, thanks for joining us today and thank you for allowing us to discuss your interesting manuscript and hopefully we'll see more of this biomarker work from you guys in the near future, perhaps published in JCO Precision Oncology.   And thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcasts.     The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

In this episode, I chat to Victoria Maskell about my biggest manifestation secret! Here we discuss all things TBM and how things have changed for me on my TBM journey. If you would like to sign up for TMB, use my code: ANNEKA to get 15% off membership. To find Victoria online: Tik Tok and Instragram: @victoria.maskell Email: victoria@victoriamaskell.com Website: victoriamaskell.com To find me online: Tik Tok: @coachingbyanneka_official Instagram: @coachingbyanneka Email: thrive@coachingbyanneka.co.uk Find all of my products on my Stan Store link below. This includes my Alcohol-Free Christmas Survival Guide, and links to apply for coaching and my other courses: https://stan.store/Coachingbyanneka

Send us a textLevi, TMB, and Marchie are here to preview the Big 12 Championship game vs. Arizona State.

No one's going hungry this week with your beloved TMBTL of the Dog hosts on the case. That's right, Lindy and Meagan have teamed up once again with Luke and Andrew of Too Beautiful to Live to bring you another episode that will take you on several journeys involving puppies in witness protection, Meagan's little buggies, Luke's homicidal tendencies, and Andrew's connection to a famous TMB earworm involving dogs, shit, and peach pits.In other words, a perfectly normal crossover event hosted by four well-adjusted adults who don't have any problems at all. New to Too Beautiful to Live? Check them out here: https://www.tbtl.net/ Do you have brain problems that would fit right in on an episode of TMBTL of the Dog? Tell us all about it deartextmeback@gmail.com. Or you can text or call us at the Best Friend Party Phone: (703) 829-0003 or DM us @textmebackpod on IG and Tiktok.Also! This is our last episode of 2024 but there will still be lots of fun things on our Patreon! Be sure to subscribe for goodies. Everyone else, we'll see your asses in 2025!STUFF TO CHECK OUT:Link to Lindy's masterclass!Gift a Lindy Cameo! She'll talk your loved one's ear off and it'll be delightful!Check out Meagan's new newsletter, SWAMP PERSON! It will make you laugh AND offer actionable insights to get us through what's coming.Subscribe to Lindy's newsletter butt newsCheck out our MERCH! (Patrons get a discount, so check us out at patreon.com/textmebackpod)⋆｡°✩⋆｡°✩⋆｡°✩⋆｡°If you like this episode and want us to keep making the show forever, please subscribe to our Patreon. This podcast will always be free, but we need your help to produce it -- and if you support our Patreon, you'll get all kinds of goodies in addition to the show itself! Learn more about the different tiers and rewards here: https://www.patreon.com/TextMeBackPodAlso! Please keep in touch with us! You can text OR CALL us at the Best Friend Party Phone: (703) 829-0003.We're on Instagram at @textmebackpod!Full videos of our episodes are on YouTube at @textlindyandmeaganbackYou can email us at deartextmeback@gmail.com!WE WANT TO HEAR FROM YOU SO BAD!⋆｡°✩⋆｡°✩⋆｡°✩⋆｡°TEXT ME BACK is a production of Lindy West and Meagan Hatcher-Mays, proud members of the BFF Network. Our senior producer is Meagan Hatcher-Mays. Our other senior producer is Lindy West. Our show is supported by COPILOT Collective and produced by Alli Slice.Our music is by Chief Ahamefule J. Oluo. Diana Bowen is our video and creative advisor. Our digital strategist is Chance Nichols.You can also follow the podcast on Instagram and TikTok @textmebackpod. And for even more bestie content, follow Lindy and Meagan on Instagram at @thelindywest and @importantmeagan!Special thanks as always to our perfect angels: Jeannie Yandel, Brandi Fullwood, and Isolde Raftery.⋆｡°✩⋆｡°✩⋆｡°✩⋆｡°See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Send us a textThis week, Levi, Marchie, and TMB are back to talk about the Cyclones' victory over Cincinnati last weekend and how Iowa State can stay alive in the Big 12 championship game race with a win at Utah this weekend. The guys also break down a number of tiebreaker scenarios so you know who to root for this weekend.

Send us a textLevi, March, and TMB are back to preview this weekend's game as your 7-0 Iowa State Cyclones control their own destiny as they work towards a Big 12 title game berth.

Following an epic Asia Trail Master Finals at TMB in Borneo, we recap the event and catch up with male champion Jeff Campbell.Check out all the footage from ATM Finals:ATM Facebook Male final Podium winners videoMale Podium:Jeff Campbell - 09:49Hisashi Kitamura - 09:51Arnie Macarenes - 09:56Female Podium:Priya Rai - 11:00Vanja Cnops - 12:36Rashila Tamang - 13:13

Send us a textThis week, Levi, Marchie, and TMB are back to kick off the 2024 football season with an analysis of the first depth chart and a preview of North Dakota, as well as our predictions for the week.

Una dieta de 1200 calorías al día es generalmente insuficiente para cualquier persona adulta por varias razones, relacionadas tanto con la salud física como mental:1. Requerimientos energéticos básicos:Tasa Metabólica Basal (TMB): La mayoría de los adultos necesitan más de 1200 calorías al día solo para mantener las funciones corporales básicas en reposo, como respirar, mantener la temperatura corporal, y la circulación sanguínea. La TMB varía según factores como la edad, el sexo, el peso, y la masa muscular, pero generalmente supera las 1200 calorías en la mayoría de las personas.Actividad diaria: Además de la TMB, el cuerpo necesita energía adicional para realizar cualquier actividad diaria, como caminar, trabajar, o realizar ejercicios. Una dieta de 1200 calorías generalmente no proporciona suficiente energía para estas actividades, lo que puede llevar a una fatiga extrema y una reducción en la capacidad para realizar tareas diarias.2. Desnutrición y deficiencias nutricionales:Insuficiencia de nutrientes esenciales: Una dieta tan baja en calorías hace difícil consumir cantidades adecuadas de nutrientes esenciales, incluyendo vitaminas, minerales, proteínas, grasas saludables, y carbohidratos. Esto puede llevar a deficiencias nutricionales que afecten la salud a corto y largo plazo, causando problemas como anemia, debilidad muscular, y debilitamiento del sistema inmunológico.Pérdida de masa muscular: Con una ingesta tan baja en calorías, el cuerpo puede comenzar a descomponer tejido muscular para obtener energía, especialmente si no se consume suficiente proteína. La pérdida de masa muscular puede disminuir el metabolismo y dificultar la pérdida de peso a largo plazo.3. Efectos psicológicos y emocionales:Relación poco saludable con la comida: Seguir una dieta tan restrictiva puede promover una relación poco saludable con la comida, llevando a comportamientos alimentarios desordenados, como el trastorno por atracón o la obsesión por la restricción.Estrés y ansiedad: La restricción calórica severa puede aumentar los niveles de estrés y ansiedad, ya que el cuerpo está constantemente en un estado de privación. Esto puede tener efectos negativos en la salud mental y en la capacidad para mantener hábitos saludables a largo plazo.4. Impacto negativo en el metabolismo:Ralentización metabólica: Cuando el cuerpo recibe menos calorías de las necesarias, entra en un "modo de ahorro de energía," reduciendo la tasa metabólica basal para conservar energía. Esto puede hacer que sea más difícil perder peso y más fácil ganarlo de nuevo una vez que se aumenta la ingesta calórica.Efecto rebote: Las dietas extremadamente bajas en calorías pueden llevar a un efecto rebote, donde la persona recupera el peso perdido, o incluso más, una vez que vuelve a una ingesta calórica normal, debido a la ralentización metabólica y la recuperación del apetito.5. Riesgos para la salud a largo plazo:Problemas hormonales: La ingesta insuficiente de calorías puede afectar el equilibrio hormonal, lo que puede causar irregularidades menstruales en mujeres, problemas de fertilidad, y otros desequilibrios hormonales.Salud cardiovascular: Una dieta insuficiente en calorías y nutrientes esenciales puede aumentar el riesgo de desarrollar problemas cardiovasculares, debido a la falta de grasas saludables y otros nutrientes importantes para la salud del corazón.En resumen, una dieta de 1200 calorías al día es generalmente insuficiente para la mayoría de los adultos porque no cubre las necesidades energéticas básicas, puede llevar a deficiencias nutricionales, afectar negativamente la salud mental, y provocar problemas metabólicos y hormonales. Es importante seguir una dieta que esté adaptada a las necesidades individuales y que promueva una relación saludable con la comida y el cuerpo.Conviértete en un seguidor de este podcast: https://www.spreaker.com/podcast/comiendo-con-maria-nutricion--2497272/support.

In this episode, Gregory Huhn, MD, MPHTM, presents a case study of a person with a long HIV treatment history, exploring when and how to consider agents with novel mechanisms of action.Listen as he discusses:The importance of engaging with patients to understand their perspectives and improve their satisfaction with their HIV careOptions in people with multiclass resistanceStudies of agents with novel mechanisms of action:BRIGHTE (fostemsavir)TMB-301/-311 (ibalizumab)CAPELLA (lenacapavir) Faculty​​Gregory Huhn, MD, MPHTM,Interim Chief, Division of Infectious DiseasesSenior Director of HIV ServicesCook County HIV Integrated ProgramsInterim Medical Director, The RMR CORE CenterProfessor, Division of Infectious DiseasesRush University Medical CenterChicago, IllinoisFollow along with the slides.https://bit.ly/4fHmxg5Get access to all of our new podcast episodes. Subscribe to the CCO Infectious Disease podcast on Apple Podcasts, Google Podcasts, or Spotify.    

Neste episódio do Arsenal de Mentores, eu conto com a ajuda do meu amigo e sócio Rafa Leite (@orafaleite), para entrevistar o grande Renato Torres (@orenatotorres), que vem fazendo coisas revolucionárias no mercado. Renato é fundador d'O Corpo Explica, da TMB e de outras empresas, e, com sua vasta experiência em tecnologia, marketing e vendas, tem estruturado processos comerciais altamente efetivos. No episódio #032, ele nos conta como saiu da falência para alcançar os sonhados lançamentos de múltiplos 8 dígitos, compartilha conosco suas vivências e ensina a estruturar times e processos comerciais que realmente dêem resultado.   Dê o play e escute agora ao episódio completo!

The 13th episode of TMB's "Weekend Hangover" with Ricky-Bobby and Dustin along with our special guest will be talking all things related to the GP races at Sachsenring. We're also planning a bit of a Laguna Seca Preview. Lets explore the story lines of the weekend. What's up with Joe Roberts and the busted wing? How about those Trackhouse dudes?? Why does MM93 suck in Q, and much much more! Lets get into it!! AND... Like always, we've got a secret special guest joining the show to weigh in. Who's it going to be?? Enjoy!! Like / Subscribe / Comment / Share..... ** ROCKWELL WATCHES: Check out their website https://rockwelltime.com/ Enter the code "TDZ20" at checkout and save 20% on a new Rockwell!! Sign up for your next TrackDaz event here: http://www.trackdaz.com *PIRELLI TIRES!! ** You can get your Pirelli rubber from us directly on our registration site. Next event is July 23rd at Laguna Seca!!. This is a bucket list track for sure, especially at the 105db limit. Lets make some noise, and have fun ripping the cork screw. Sign up here: http://www.trackrabbit.com/s/2kxu Follow us on Facebook: / trackdaz Follow us on Instagram: @trackdaz Follow the TrackDaz Crew: @chili144 @jimmyz853 @phen2210 @gil823 @formula_r @chili144 @lgbrown_ @dkm60 @canea121 @g_offsims @ricardo.abueg @trackdazkaren @fharo3 @modbaez @m39023 @dreek46 @bubblesrides @r6_krissy_P

Welcome back Cyclone fans! The 2024 season is upon us, and Levi, Marchie, and TMB are back to analyze the Iowa State roster.

This episode of TMB's "Weekend Hangover" with Ricky-Bobby and Dustin has reached 12 episodes already!! Crazy!! We're planning chat about all of the racing storylines of the weekend. Topics include the MotoGP and Rookies Cup races at Assen, along with MotoAmerica races at the Ridge. Lets get into it!! AND... Like always, we've got a secret special guest joining the show to weigh in. Who's it going to be?? Enjoy!! Like / Subscribe / Comment / Share..... ** ROCKWELL WATCHES: Check out their website https://rockwelltime.com/ Enter the code "TDZ20" at checkout and save 20% on a new Rockwell!! Sign up for your next TrackDaz event here: http://www.trackdaz.com *PIRELLI TIRES!! ** You can get your Pirelli rubber from us directly on our registration site. Next event is July 23rd at Laguna Seca!!. This is a bucket list track for sure, especially at the 105db limit. Lets make some noise, and have fun ripping the cork screw. Sign up here: http://www.trackrabbit.com/s/2kxu Follow us on Facebook: / trackdaz Follow us on Instagram: @trackdaz Follow the TrackDaz Crew: @chili144 @jimmyz853 @phen2210 @gil823 @formula_r @chili144 @lgbrown_ @dkm60 @canea121 @g_offsims @ricardo.abueg @trackdazkaren @fharo3 @modbaez @m39023 @dreek46 @bubblesrides @r6_krissy_P

This is the 11th episode of TMB's "Weekend Hangover" with Ricky-Bobby and Dustin. In this one, we chat about all of the racing storylines of the weekend. Topics include the WorldSBK action at Misano.. Is Toprak superman? In MotoAmerica its the Bobby, Mathew, Hayden Show for the most part. Lets get into it!! AND... Like always, we've got a secret special guest joining the show to weigh in. Who's it going to be?? Enjoy!! Like / Subscribe / Comment / Share..... ** ROCKWELL WATCHES: Check out their website https://rockwelltime.com/ Enter the code "TDZ20" at checkout and save 20% on a new Rockwell!! Sign up for your next TrackDaz event here: http://www.trackdaz.com *PIRELLI TIRES!! ** You can get your Pirelli rubber from us directly on our registration site. Next event is June 29-30th weekend. We're going to do Config 13 CW Saturday, and Config 1 CCW on Sunday. Saturday night is also a Motorbike swap meet!! Sign up here: http://www.trackrabbit.com/s/2ksi Follow us on Facebook: / trackdaz Follow us on Instagram: @trackdaz Follow the TrackDaz Crew: @chili144 @jimmyz853 @phen2210 @gil823 @formula_r @chili144 @lgbrown_ @dkm60 @canea121 @g_offsims @ricardo.abueg @trackdazkaren @fharo3 @modbaez @m39023 @dreek46 @bubblesrides @r6_krissy_

the 10th episode of TMB's "Weekend Hangover" with Ricky-Bobby and Dustin. In this one, we chat briefly on the MotoAmerica races at Road America, Rookies Cup, and of course all the GP stuff. Joe Roberts showing American riders kick ass, MotoGP Musical Chairs, Rain and Sunshine in Cheeseland... of course we'll talk Baggers!! Oh, and we've got a special guest like always! Like/Subscribe/Comment/Share/ all that, but most importantly, enjoy. ** ROCKWELL WATCHES: Check out their website https://rockwelltime.com/ Enter the code "TDZ20" at checkout and save 20% on a new Rockwell!! Sign up for your next TrackDaz event here: http://www.trackdaz.com *PIRELLI TIRES!! ** You can get your Pirelli rubber from us directly on our registration site. Next event is June 29-30th weekend. We're going to do Config 13 CW Saturday, and Config 1 CCW on Sunday. Saturday night is also a Motorbike swap meet!! Sign up here: http://www.trackrabbit.com/s/2ksi Follow us on Facebook: / trackdaz Follow us on Instagram: @trackdaz Follow the TrackDaz Crew: @chili144 @jimmyz853 @phen2210 @gil823 @formula_r @chili144 @lgbrown_ @dkm60 @canea121 @g_offsims @ricardo.abueg @trackdazkaren @fharo3 @modbaez @m39023 @dreek46 @bubblesrides

Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss promising combination therapies and other compelling advances in genitourinary cancers in advance of the 2024 ASCO Annual Meeting. TRANSCRIPT Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I'm the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News. I'm delighted to be joined by Dr. Jeanny Aragon-Ching, a GU medical oncologist and the clinical program director of genitourinary cancers at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing some key abstracts in GU oncology that will be featured at the 2024 ASCO Annual Meeting.  Our full disclosures are available in the transcript of this episode. Jeanny, it's great to have you on the podcast. Dr. Jeanny Aragon-Ching: Thank you so much, Dr. Agarwal. It's a pleasure to be here. Dr. Neeraj Agarwal: So, Jeanny, let's start with some bladder cancer abstracts. Could you tell us about the Abstract 4509 titled, “Characterization of Complete Responders to Nivolumab plus Gemcitabine Cisplatin versus Gemcitabine Cisplatin Alone in Patients with Lymph Node Only Metastatic Urothelial Carcinoma from the CheckMate 901 Trial.”  Dr. Jeanny Aragon-Ching: Of course, Neeraj, I would be delighted to. First, I would like to remind our listeners that the CheckMate 901 trial was a randomized, open-label, phase 3 study, in which this particular sub-study looked at cisplatin-eligible patients with previously untreated, unresectable, or metastatic urothelial carcinoma who were assigned to receive the combination of gemcitabine and cisplatin, followed by up to 2 years of nivolumab or placebo. Based on the data presented at ESMO 2023 and subsequently published in the New England Journal of Medicine, which shows significantly improved progression-free survival and overall survival in patients receiving the combination of gemcitabine, cisplatin, and nivolumab, this regimen was approved in March 2024 as a first-line therapy for patients with unresectable or metastatic urothelial carcinoma.  In the abstract that will be featured at ASCO this year, Dr. Matt Galsky and colleagues present a post-hoc analysis that aims to characterize a subset of patients with complete response as well as those with lymph node-only metastatic disease. In patients receiving the experimental treatment, 21.7% achieved a complete response, while 11.8% of the patients in the control arm achieved a complete response.  Among these complete responders, around 52% had lymph- node-only disease in both arms. Furthermore, when characterizing the subgroup of patients with lymph-node-only disease, those receiving the combination of gemcitabine-cisplatin plus nivolumab had a 62% reduction in the risk of progression or death and a 42% reduction in the risk of death compared to those treated with gemcitabine-cisplatin alone.  The median overall survival in the experimental arm in this subgroup was around 46.3 months, while it was only 24.9 months in the control arm. The ORR in patients with lymph-node-only disease receiving gem-cis plus nivo was about 81.5% compared to 64.3% in those treated with gem-cis alone. Dr. Neeraj Agarwal: Thank you, Jeanny, for the excellent summary of this abstract. We can say that nivolumab plus gemcitabine-cisplatin induced durable disease control and clinically meaningful improvements in OS and PFS compared to gem-cis alone in patients with lymph- node-only metastasis, and deserves to be considered as one of the options for these patients.  In a similar first-line metastatic urothelial carcinoma setting, Abstract 4502, also reported data on a recently approved combination of enfortumab vedotin and pembrolizumab. Can you tell us more about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Sure, Neeraj. So, as quick reminder to our audience, this regimen was tested in the EV-302 phase 3 trial, where patients with previously untreated, locally advanced or metastatic urothelial carcinoma were randomized to receive enfortumab vedotin, plus pembrolizumab or gemcitabine plus either cisplatin or carboplatin. These data were also first presented at ESMO 2023 and subsequently published in the New England Journal of Medicine. They showed that this immune based combination significantly improved both progression free survival and overall survival, which were the primary endpoints compared to chemotherapy. In this abstract, Dr. Shilpa Gupta from the Cleveland Clinic and colleagues present the results of patient reported outcomes based on quality-of-life questionnaires in this trial.  Time to pain progression and time to confirm deterioration were numerically longer in patients treated with EV plus pembro, and patients with moderate to severe pain at baseline receiving this combination had a meaningful improvement in the Brief Pain Inventory Short-Form worst pain from week 3 through 26. Dr. Neeraj Agarwal: Thank you, Jeanny. This means that patients treated with EV plus pembro did not only have improved survival compared with platinum-based chemotherapy, but also improvement in their quality-of-life and functioning, further supporting the value of this combination for patients with locally advanced or metastatic urothelial carcinoma. This is terrific news for all of our patients.   Before we wrap up the bladder cancer section, would you like to tell our listeners about Abstract 4565, which provides the data on the efficacy of trastuzumab deruxtecan in patients with bladder cancer? Dr. Jeanny Aragon-Ching: Yes, Neeraj; this is timely given the recent FDA approval, which we will talk about. The abstract is titled, “Efficacy and Safety of Trastuzumab Deruxtecan in Patients with HER2 Expressing Solid Tumors: Results from the Bladder Cohort of the DESTINY-PanTumor02 Study.” And as a quick reminder, the DESTINY-PanTumor02 was a phase 2 open-label study where trastuzumab deruxtecan, an antibody-drug conjugate targeting HER2 expression on cancer cells, was evaluated in patients with HER2-expressing locally advanced or metastatic disease who previously received systemic treatment or who had no other treatment options. The expression of HER2 was evaluated on immunohistochemistry by local or central testing.   The primary endpoint was confirmed objective response rate by investigator assessment. Secondary endpoints included duration of response, progression free survival, disease control rate, and safety. The primary analysis, which was published in the Journal of Clinical Oncology, showed an ORR of 37.1% and responses across all cohorts and the median duration of response was 11.3 months. Based on these results, fam-trastuzumab deruxtecan-nxki was just granted accelerated FDA approval for unresectable or metastatic HER2-positive solid tumors in April 2024.  So, back to this abstract; Dr. Wysocki and colleagues report the results of the bladder cancer cohort. This study included 41 patients with urothelial cancer and at a median follow up of around 12.6 months, the objective response rate among these patients was 39%, the median PFS was 7 months, and the duration of response median was 8.7 months. The disease control rate at 12 weeks was around 71%. Regarding the safety profile, 41.5% of patients experienced grade ≥3 drug related adverse events and interstitial lung disease or pneumonitis did occur in about 4 patients. Although there was no statistical comparison between different groups, the ORR was numerically highest among the HER2 3+ group with 56.3%.  Dr. Neeraj Agarwal: Thank you, Jeanny. So, these data support consideration of trastuzumab deruxtecan as a salvage therapy option for pre-treated patients with HER2 expressing urothelial cancers and show that we are extending our treatment options to include therapies with novel mechanisms of action. This is definitely exciting news for patients with bladder cancer. Dr. Jeanny Aragon-Ching: Yes, absolutely, Neeraj. Now, let's switch gears a bit to prostate cancer. Could you tell us about Abstract 5005 which is titled, “EMBARK Post Hoc Analysis of Impact of Treatment Suspension on Health Quality-of-Life?” Dr. Neeraj Agarwal: Of course, I'd be happy to. So, enzalutamide was recently granted FDA approval for the treatment of patients with non-metastatic castration-sensitive prostate cancer with biochemical recurrence at high-risk of metastasis, based on the results of the EMBARK trial, which was a phase 3 study where patients with high-risk biochemical recurrence were randomized to receive either enzalutamide with leuprolide, enzalutamide monotherapy, or placebo plus leuprolide. The primary endpoint was metastasis-free survival with secondary endpoints including overall survival and safety.  Results showed that patients receiving enzalutamide alone or enzalutamide plus leuprolide had significantly improved metastasis-free survival compared to those treated with leuprolide alone while preserving health-related quality-of-life.   One important aspect in the design of the trial was that patients who achieved undetectable PSA at week 37 underwent treatment suspension. The treatment was resumed if PSA rose to more than 2 ng/ml for patients who underwent radical proctectomy or when PSA rose to more than 5 ng/ml for those who did not undergo surgery.  In this abstract, Dr. Stephen Freedland and colleagues present a post-hoc analysis of health-related quality-of-life outcomes after treatment suspension between weeks 37 and 205. They found that treatment was suspended in 90.9% of patients receiving enzalutamide plus leuprolide, 85.9% of those receiving enzalutamide monotherapy, and 67.8% of those receiving leuprolide monotherapy. Among those patients who stayed on treatment suspension, a trend toward numerical improvement in health-related quality-of-life after week 37 was seen in all 3 arms and this reached clinically meaningful threshold at week 205 in pain questionnaires, physical well-being, urinary and bowel symptoms. For hormonal treatment side effects, all arms reached clinically meaningful improvement at the subsequent assessments of week 49 to week 97. However, patients slowly deteriorated, with clinically meaningful deterioration at week 205 relative to week 37 in patients receiving the combination of enzalutamide and leuprolide and those treated with leuprolide.    Concerning sexual activity, a clinically meaningful improvement was reported only in patients receiving enzalutamide plus leuprolide, possibly because sexual function was better preserved prior to suspension in the enzalutamide monotherapy arm and thus there was less opportunity for “improvement” while on suspension.  Dr. Jeanny Aragon-Ching: Thank you, Neeraj, for this great summary. This analysis confirms that treatment suspension in good responders might lead to a clinically meaningful improvements in health-related quality-of-life.   Now, moving on to patients with metastatic castration-resistant prostate cancer, what can you tell us, about Abstract 5008 titled, “Baseline ctDNA analyses and associations with outcomes in taxane-naive patients with mCRPC treated with 177Lu-PSMA-617 versus change of ARPI in PSMAfore”?  Dr. Neeraj Agarwal: Sure, Jeanny. The PSMAfore trial was a phase 3 study that compared the efficacy of 177Lu-PSMA-617 versus an ARPI switch in patients with mCRPC and prior progression on a first ARPI, and not previously exposed to docetaxel chemotherapy. The primary endpoint was rPFS and OS was an important secondary endpoint. The primary analysis presented at ESMO 2023 showed a significantly prolonged rPFS in patients receiving lutetium. In the abstract that will be featured at the 2024 ASCO Annual Meeting, Dr. Johann De Bono and colleagues present an exploratory analysis regarding the associations between baseline circulating tumor DNA and outcomes.  ctDNA fraction was evaluated in all samples as well as alterations in key prostate cancer drivers prevalent in more than 10% of participants.  The investigators sought to interrogate the association of ctDNA fraction or alterations with rPFS, PSA response, and RECIST response at data cutoff. They showed that median rPFS was significantly shorter in patients with a ctDNA fraction >1% compared to those with a fraction < 1% regardless of the treatment arm. Furthermore, ctDNA fraction >1% was also associated with worst RECIST response and PSA50 response. Regarding prostate cancer drivers, median rPFS was significantly shorter in patients with alterations in the AR, TP53 or PTEN in both treatment arms. There was no significant association between ctDNA alterations and PSA or objective responses. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So, these results show that the presence of a ctDNA fraction >1% or alterations in AR, P53 and PTEN were all associated with worse outcomes regardless of treatment with lutetium or change in the ARPI. These data are definitely important for counseling and prognostication of patients in the clinic and may guide the design of future clinical trials. Let's move on to kidney cancer. Neeraj, do you have any updates for us?  Dr. Neeraj Agarwal:  Sure. In Abstract 4512 titled, “A Multi-institution Analysis of Outcomes with First-Line Therapy for 99 Patients with Metastatic Chromophobe Renal Cell Carcinoma,” Dr. Sahil Doshi and colleagues present a retrospective, multi-institutional study comparing survival outcomes, including time-to-treatment failure and overall survival, between different first-line treatment options in patients with metastatic chromophobe renal cell carcinoma, where limited clinical trial data exists to guide systemic therapy. They categorized patients into 4 treatment groups: and immune checkpoint inhibitors + targeted therapy doublets (such as ICI VEGF TKI); pure immune checkpoint inhibitor monotherapy and doublets (such as ipilimumab plus nivolumab); targeted therapy doublets (such as lenvatinib plus everolimus), and targeted monotherapy (such as sunitinib).  They identified 99 patients, of whom 54 patients received targeted monotherapy, 17 received ICI VEGF-TKI, 14 received targeted doublet, and 14 patients received only ICI therapies. So the patients treated with any doublet containing a targeted agent had a 52% decrease in the risk of treatment failure and a 44% decrease in the risk of death compared to those treated with targeted monotherapy. The median time to treatment failure was 15 months with IO-targeted doublet, and the median overall survival was 56 months. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So, these results show that targeted doublet regimens resulted in a longer time to treatment failure and overall survival compared to any monotherapy in patients with chromophobe metastatic RCC and definitely provides valuable insights on treatment selection, albeit I would say there's still a small number of patients that were included in this retrospective analysis. Dr. Neeraj Agarwal: I completely agree this is a relatively small number of patients, but I decided to highlight the abstract given how rare the cancer is, and it is highly unlikely that we'll see large randomized clinical trials in patients with metastatic chromophobe renal cell carcinoma.  So, before we wrap up the podcast, what would you like to tell us about Abstract 5009 which is titled, “A Phase II Trial of Pembrolizumab Platinum Based Chemotherapy as First Line Systemic Therapy in Advanced Penile Cancer: HERCULES (LACOG 0218) Trial.” Dr. Jeanny Aragon-Ching: I'm glad you brought this up, Neeraj. As our listeners may know, advanced penile squamous cell carcinoma has a poor prognosis with limited treatment options. From this perspective, the results of the LACOG 0218 trial are very important. As you mentioned, this was a phase 2 single-arm study evaluating the addition of pembrolizumab to platinum-based chemotherapy as first-line treatment in patients with metastatic or locally advanced penile squamous cell carcinoma not amenable to curative therapy. Patients enrolled received chemotherapy, namely 5-Fluorouracil with cisplatin or carboplatin and pembrolizumab 200 mg IV every 3 weeks for 6 cycles, followed by pembrolizumab 200 mg IV every 3 weeks up to 34 cycles. The primary endpoint was confirmed overall response rate by investigator assessment.  In the 33 patients eligible for the efficacy analysis, the confirmed ORR by investigator assessment was 39.4% and included one complete response and 12 partial responses. The confirmed ORR was 75% in patients with high TMB and 55.6% in patients positive for HPV16, making TMB and HPV16 potential predictive biomarkers for efficacy in this study. Concerning the toxicity profile, any grade treatment-related adverse events were reported in around 92% of patients, and grade 3 or more treatment-related adverse events occurred in 51% of patients. 10.8% of patients discontinued treatment due to adverse events.  Dr. Neeraj Agarwal: Thank you, Jeanny. I would like to add that HERCULES is the first trial to demonstrate the efficacy of an immune checkpoint inhibitor in advanced penile squamous cell carcinoma with a manageable safety profile. Thus, the combination of ICI with platinum-based chemotherapy is a promising treatment for advanced penile squamous cell carcinoma and warrants further investigation.  Dr. Jeanny Aragon-Ching: I agree, Neeraj. Any final remarks before we conclude today's podcast? Dr. Neeraj Agarwal: Jeanny, I really want to thank you for your participation and valuable insights. Your contributions are always appreciated, and I sincerely thank you for taking the time to join us today. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. It was a pleasure.  Dr. Neeraj Agarwal:  As we bring this podcast to an end, I would like to acknowledge the significant advances happening in the treatment of patients with genitourinary cancers. During our upcoming 2024 ASCO Annual Meeting, there will be an array of different studies featuring practice-changing data presented by researchers and physicians from around the globe. I urge our listeners to not only participate in this event to celebrate these achievements, but to also play a role in sharing these cutting-edge data with healthcare professionals worldwide. Through our collective efforts, we can surely optimize the benefits of patients on a global scale.   And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcast. Thank you very much.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's speakers:  Dr. Neeraj Agarwal  @neerajaiims  Dr. Jeanny Aragon-Ching    Follow ASCO on social media:   @ASCO on Twitter     ASCO on Facebook     ASCO on LinkedIn       Disclosures:    Dr. Neeraj Agarwal:     Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences    Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas     Dr. Jeanny Aragon-Ching:  Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono  Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis,   Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics. 

Second Episode of the new TMB series called "Weekend Hangover" where TMB host Dustin Coyner, and "Ricky" Bobby Leavitt discuss the past weekend's races. This past weekend MotoGP happened under the lights at Qatar, while MotoAmerica was running the Daytona 200. I'm sure there's lots of crap to talk about all sorts of subjects. Enjoy! Please Like/share/subscribe/comment all that stuff... ** Sign up for your next TrackDaz event here: http://www.trackdaz.com Next event is April 20-21 WEEKEND at Thunderhill's west track http://www.trackrabbit.com/s/2kmm *PIRELLI TIRES!! ** You can get your Pirelli rubber from us directly on our registration site. Follow us on Facebook: / trackdaz Follow us on Instagram: @trackdaz Follow the TrackDaz Crew: @chili144 @jimmyz853 @phen2210 @gil823 @formula_r @chili144 @lgbrown_ @dkm60 @canea121 @g_offsims @ricardo.abueg @r6_krissy_ @trackdazkaren @fharo3 @modbaez @m39023 @dreek46 @bubblesrides

In this episode, we welcome Emmy-nominated Composer, Score Producer and Musician Chris Ruggiero. Chris has worked on films such as Emily the Criminal, Swallow, The Martha Mitchell Effect, Minding the Gap, Hooligan Sparrow, “Soundbreaking: Stories from the Cutting Edge of Recorded Music,” One Child Nation, Plan C, Camp Courage, episodes of “American Masters" and “American Experience” — and Resynator, which is premiering at SXSW this month. In our chat, we hear Chris' backstory, his path from working at MTV, to creating jingles for brands, on through scoring many of today's top independent films and documentaries. The Making Of is presented by AJA Video Systems.Versatile color management and conversion with AJA ColorBox From film to live production, color is an art. Achieving the right look requires a combination of talent and access to tools like AJA ColorBox. The color management and conversion box has quickly become a favorite among DITs with camera log, HDR, and WCG support, 12G-SDI and HDMI 2.0 connectivity, and unparalleled color processing. Find out why.ZEISS Conversations with Meena SinghJoin the ZEISS Conversations webinar featuring renowned Director of Photography Meena Singh on Thursday, March 28th at 12pm PST / 3pm EST. Hear her insights about using ZEISS Supreme Prime Radiance lenses to create the look for the notable romantic comedy film, "Wedding Season." They will also discuss how she created the visual language for Sundance 2024 selected short film “Guts” and several documentary projects. Sign up for free hereMovie Book of the Month: Space Odyssey: Stanley Kubrick, Arthur C. Clarke, and the Making of a MasterpieceThis is the definitive story of the making of 2001: A Space Odyssey, acclaimed today as one of the greatest films ever made, including the inside account of how director Stanley Kubrick and writer Arthur C. Clarke created this cinematic masterpiece. Author Michael Benson explains how 2001 was made, telling the story primarily through the two people most responsible for the film, Kubrick and science fiction legend Arthur C. Clarke. Benson interviewed Clarke many times, and has also spoken at length with Kubrick's widow, Christiane; with visual effects supervisor Doug Trumbull; with Dan Richter, who played 2001's leading man-ape; and many others.A colorful nonfiction narrative packed with memorable characters and remarkable incidents, Space Odyssey provides a 360-degree view of this extraordinary work, tracking the film from Kubrick and Clarke's first meeting in New York in 1964 through its UK production from 1965-1968, during which some of the most complex sets ever made were merged with visual effects so innovative that they scarcely seem dated today. A concluding chapter examines the film's legacy as it grew into it current justifiably exalted status. Available hereFrom our Friends at Broadfield…The Atomos Ninja bundled with Atomos Connect combines the newest 5" monitor/recorder & playback device with the latest Atomos Cloud features enabled by Atomos Connect. The free 6-month subscription to Atomos Cloud Studio enables camera-to-cloud, remote collaboration and review, cloud editing, live production and streaming. This complete solution will even include an accessory kit with rechargeable batteries, fast-charger, screen protector, travel case and more!Browse hereResource of the Month: The Daily Drop“The Daily Drop” is all about the tech, craft and business of producing content. The ongoing daily series (Mon-Fri) from Jem Schofield of theC47 focuses on video production and filmmaking with a core focus on education.Here's a recent episode that give's Jem's initial thoughts on OpenAI's Sora and how it might impact our industry…More episodes available here Upcoming L.A. Event:Cinelease Open HouseCinelease, known for providing the industry's most extensive array of grip, electrical and lighting equipment and full-service studios, opens its doors for a day of talks, tech, live music, games, food truck favorites, drafts & sodas, and out of this world presentations. The festivities run from noon to 8pm on March 16, 2024 at Cinelease headquarters in Los Angeles.Cinelease has lined up something for everyone at their let-your-hair-down Open House: Cutting-edge tech from AC Lighting, ACT (AC Power), Aputure, ARRI, Camera Car, Creamsource, Elation, Illumination Dynamics, INDU, InnerCircle, Jagoteq, JL Fisher, K5600, Kino Flo, KOTO, LA North Studios, LiteGear, Leitz, Lightscape, LRX, Maccam, Matthews Studio Equipment, NBCUniversal / Cineo, Nanlux, Osram, Power Gems, Roe Visuals, Rosco, RST Visions in Color, Sony, Sumolight, TRP, RT Pro, TMB and more. Learn more hereFeatured NYC Event: Cine Gear NY | March 14-16, 2024Mark your calendars for March and head on out to the thriving Industry City complex along the Brooklyn Upper Bay waterside. Cine Gear's studio-style event is gathering steam as state-of–the-art technology brands are preparing to reveal their latest & greatest gear in the historic Paper Factory Hall. New this year is Photo Focus, a one-day educational event dedicated to the art and craft of Still Photography.Get your Free Passes herePodcast Rewind:Feb. 2024 - Ep. 26…The Making Of is published by Michael Valinsky.If you'd like to promote your company to over 11,500 leading film & TV pros reading this newsletter, please email us at: mvalinsky@me.com Get full access to The Making Of at themakingof.substack.com/subscribe

New TMB series called "Weekend Hangover" where TMB host Dustin Coyner, and "Ricky" Bobby Leavitt discuss the past weekend's races. This past weekend was the season opener of World SBK. We'll discuss everything SBK, which riders surprised people, which ones disappointed, drama in the races, etc.. Also we'll touch a bit on the World SS races, and even the Australian SBK races which were taking place that same weekend. Enjoy! It was fun chatting with these goons, hope you enjoy. Next TrackDaz events March 1 at Buttonwillow with the Attack Yamaha boys Next event is: Friday, March 1st Sign up here: https://tinyurl.com/AttackYamahaMarch1 March 23-24 at Thunderhill West Track. Sign up here: https://tinyurl.com/MarchTHillWest Please Like/share/subscribe/comment all that stuff... ** Sign up for your next TrackDaz event here: http://www.trackdaz.com **PIRELLI TIRES!! *** You can get your Pirelli rubber from us directly on our registration site. Follow us on Facebook: / trackdaz Follow us on Instagram: @trackdaz Follow the TrackDaz Crew: @chili144 @jimmyz853 @phen2210 @gil823 @formula_r @chili144 @lgbrown_ @dkm60 @canea121 @g_offsims @ricardo.abueg @trackdazkaren @fharo3 @modbaez @m39023 @dreek46 @bubblesrides

In today's episode of Backpacker Radio presented by The Trek, we are once again loving love. That's right, it's the 4th edition of our Valentine's Day-themed show. Today we catch up with Wesley and Marie Black, known on trail as Yeti Legs and Basecamp. Less than two years after meeting, they were not only married but together taking on a thru-hike of the PCT. Wesley and Marie pull no punches in sharing the nitty-gritty of making a relationship work during a thru-hike and are especially candid about their on-trail sex life including their hygiene practices, foreplay, what they use for lubrication, best positions in a tent, and more. This one is entertaining, enlightening, and slightly erotic. Strap in. We wrap the show with what we would do if we could be our significant other for a day, the triple crown of petty fights we have with our partners, Marie shares a plastic melting shit story, and Chaunce has a very dumb stupid thing of the week. Ka'Chava: Get 10% off at kachava.com/backpacker. Gossamer Gear: Use code “DINGLEBERRY” for 20% off packs at gossamergear.com.  [divider] Interview with Wes & Marie Wes & Marie's Instagram Wes & Marie's Linktree Time stamps & Questions 00:04:55 - Reminders: Last call to apply for the BPR internship, Tyvek wall goes on sale next week, and the Badger Sponsorship launched today! 00:09:35 - Introducing Wes & Marie 00:11:40 - Story of how Wes & Marie met 00:14:30 - When did you get engaged? 00:19:42 - Did you have any concerns about getting engaged so quickly? 00:24:00 - Did you have any doubts in the first six months? 00:26:01 - Do you have baby fever? 00:28:53 - What led to deciding to thru-hike together? 00:32:05 - What outdoor experience did you have before meeting each other? 00:35:30 - How did you transition from running to hiking? 00:38:16 - When did you realize you had a lot of heavy gear? 00:40:30 - What was it like hiking in a high snow year? 00:43:28 - How did your mileage change between the desert and the Sierras? 00:44:50 - What did you learn about each other on the PCT you didn't know before? 00:50:40 - How did you handle the time stress? 00:56:20 - Tell us about your career in film 01:01:25 - What were your best fights on trail? 01:13:20 - What other tips do you have for couples on trail? 01:15:12 - What's your sex life like on trail? 01:18:32 - What are your tips for having great sex on trail? 01:24:27 - Did you bring any toys? 01:26:00 - Why didn't you have sex during the day? 01:27:23 - Did you take any of your PCT lessons into the Tour du Mont Blanc or the CT? 01:29:24 - Raise the shoe game! 01:47:44 - Tell us about the Colorado Trail hike 01:52:50 - Fuck Marry Kill: PCT, TMB, CT 01:54:40 - Will you share one of your favorite hidden gem hikes? 01:56:11 - Tell us about your podcast 01:58:35 - Tell us about how you met Dirt Diva Segments Trek Propaganda: The Ultimate Guide to Thru-Hiking Electronics by Alex “GPS” Brown QOTD: If you could wake up and be your significant other for a day, what would you do that day? Stupid Thing of the Week Triple Crown of petty fights you have with your partner Gross or Not Gross Mail Bag 5 Star Review [divider] Check out our sound guy @paulyboyshallcross. Leave us a voicemail! Subscribe to this podcast on iTunes (and please leave us a review)!  Find us on Spotify, Stitcher, and Google Play. Support us on Patreon to get bonus content. Advertise on Backpacker Radio Follow The Trek, Chaunce, Badger, and Trail Correspondents on Instagram. Follow Backpacker Radio, The Trek and Chaunce on YouTube. Follow Backpacker Radio on Tik Tok.  Our theme song is Walking Slow by Animal Years. A super big thank you to our Chuck Norris Award winner(s) from Patreon: Alex & Misty with Navigators Crafting, Andrew, Austen McDaniel, Austin Ford, Brad & Blair (Thirteen Adventures), Brent Stenberg, Bryan Alsop, Christopher Marshburn, Coach from Marion Outdoors, Dayne, Derek Koch, Eric Casper, Erik Hofmann, Greg Knight, Greg McDaniel may he bring honor to his name, Ironhike endurance productions, Jason “Snail” Snailer, Liz Seger, Patrick Cianciolo, Sawyer Products, SPAM, Timothy Hahn, and Tracy “Trigger” Fawns. A big thank you to our Cinnamon Connection Champions from Patreon: 12 Trees Farms, Dcnerdlet, Emily Galusha, Hailey Buckingham, Jeanie, Jeanne Latshaw, Jeff LaFranier, Joann Menzer, Keith Dobie Jr, Peter, and Ruth S.

The Texas Medical Board clarifies new fingerprinting requirement ahead of February license renewals. Get instructions and details at the TMB website. Read the TMT article at www.texmed.org/TMT.

Bienvenidos a un nuevo episodio de #NaturalmenteSascha Este es uno de los episodios más solicitados: ¡hablamos sobre la pérdida de grasa! Después de unas festividades donde podemos tener desorden en la alimentación y hacer menos ejercicio, sé que muchos están listos para retomar un estilo de vida más saludable. La pérdida de grasa es un proceso que requiere paciencia y un plan adaptado a cada uno En este episodio, comparto una fórmula específica que te ayudará a calcular un número de calorías en mantenimiento utilizando la Fórmula de Harris-Benedict. Además, te explico cómo ajustar este valor según tu nivel de actividad. Fórmula de Harris-Benedict: - Para hombres: TMB = 88.362 + (13.397 x peso en kg) + (4.799 x altura en cm) - (5.677 x edad en años) - Para mujeres: TMB = 447.593 + (9.247 x peso en kg) + (3.098 x altura en cm) - (4.330 x edad en años) Una vez que obtengas tu TMB (Tasa Metabólica Basal), puedes multiplicarlo por un factor de actividad para determinar las calorías en mantenimiento. Por ejemplo: - Sedentario (poco o ningún ejercicio): TMB x 1.2 - Ligera actividad (ejercicio ligero o práctica deportiva 1-3 días a la semana): TMB x 1.375 - Moderada actividad (ejercicio moderado o práctica deportiva 3-5 días a la semana): TMB x 1.55 - Alta actividad (ejercicio intenso o práctica deportiva 6-7 días a la semana): TMB x 1.725 - Muy alta actividad (ejercicio muy intenso o trabajo físico): TMB x 1.9 Recuerda, cada persona es única y debe elegir lo que mejor se adapte a su estilo de vida, hoy te cuento algunas estrategias que puedes considerar para lograr la pérdida de grasa deseada. Suscríbete al canal ¡y no te pierdas un nuevo episodio todos los lunes! ¿De qué te gustaría que hablemos en los próximos episodios? Cuéntame en los comentarios. ¡Nos vemos pronto! Contacto Laboral: info@saschafitness.com Nos leemos en mis redes sociales: Website saschafitness.com Instagram instagram.com/saschafitness Youtube youtube.com/@SaschaFitnessTV?si=GmFzFqVwkVAWL3_l Facebook facebook.com/saschafitnessoficial/?fref=ts Twitter twitter.com/saschafitness

"We come to it at last, the great podcast of our time." - Gandalf, sort of Intrepid hosts Lindy and Meagan battle common dismissals of the fantasy genre and tell us what they love and don't love about the beloved series The Lord Of The Rings. And speaking of beloved, would you marry Gimli or Aragorn? Kill Frodo or Pippin? The hosts play the most epic game of Eff Marry Kill you've ever heard with the heroes from the Fellowship Of The Ring. And finally - Lindy and Meagan make TMB history with their very first guest ever. May this episode be a light to you in dark places, when all other lights go out.  Send us your accolades! Text B-F-F to 206-926-9955 to join the Text Me Back Text Club, or email us at textmeback@kuow.org   See omnystudio.com/listener for privacy information.

Amy welcomes Ericka Young, the CEO of Tailor-Made Budgets, to the Including You podcast to discuss financial wellness. TMB provides Financial Wellness Education as an employee benefit for small- to midsize organizations. Connect with Ericka on LinkedIn. https://bit.ly/3tFIs3I Check out Ericka's website. https://bit.ly/46Pj4qM Including You is brought to you by Lead at Any Level. Learn more about them on their website. http://bit.ly/2lPvOMM Learn more about Pfizer on their website. https://bit.ly/2TTtZiZ Listen to Pfizer's "Science Will Win" podcast. https://bit.ly/3u3uoxW

Where do oral medicine specialists fit in the world of oral surgery? Here on the Everyday Oral Surgery Podcast is the oral medicine specialist, Dr. Hayley Vatcher to answer this question! Tuning in, you'll hear all about Hayley's career, the process of becoming an oral medicine specialist, the types of patients she gets, what treatment she offers, how she treats TMB, all about autoimmune conditions she sees and how she treats them, and so much more! We even delve into some interesting topics such as the emotional factors involved in oral conditions and how diet plays a role in health conditions. Finally, our guest answers our rapid-fire questions. You don't want to miss this one so press play now!Key Points From This Episode:A warm introduction to today's guest, Dr. Hayley Vatcher. Hayley tells us about what led her to oral medicine and what her practice setup is like now. Where she fits into oral surgery as an oral medicine specialist. The types of patients Hayley gets and the treatments she offers. The different ways Hayley treats TMB and the main contributing factor that may cause it. The emotional factors in oral medicine and why Haley uses animal-assisted therapy. Autoimmune conditions she sees (like Sjogren's syndrome) and how she treats them. How much diet plays a role in autoimmune conditions and other medical conditions.Hayley talks about the process of becoming an oral medicine specialist. Hayley shares the best book she's read this year. Why exercise is so beneficial for Haley's oral medicine career. Hayley shares her favorite movies and TV series and her favorite quote.Links Mentioned in Today's Episode:Dr. Hayley Vatcher Email Address — hvatcher@gmail.comDr. Hayley Vatcher on LinkedIn — https://www.linkedin.com/in/hvatcher/Charleston Oral and Facial Surgery — https://www.charlestonoralandfacialsurgery.com/KLS Martin — https://www.klsmartin.com/The Plant Paradox — https://www.amazon.com/Plant-Paradox-Dangers-Healthy-Disease/dp/006242713X/Oral and Maxillofacial Pathology — https://www.amazon.com/Oral-Maxillofacial-Pathology-Brad-Neville/dp/0323789811/refEveryday Oral Surgery Website — https://www.everydayoralsurgery.com/ Everyday Oral Surgery on Instagram — https://www.instagram.com/everydayoralsurgery/ Everyday Oral Surgery on Facebook — https://www.facebook.com/EverydayOralSurgery/Dr. Grant Stucki Email — grantstucki@gmail.comDr. Grant Stucki Phone — 720-441-6059

The Sons start the show by recapping the first few weeks of fall camp, including a look at what they know, and what they don't know so far. This sparked a UCF Mike Top 5 list of things UCF fans lie about, which sprung into conversations about the cows, Lubbock, Soccer, and OAKAAK. However, the biggest lie, according to Mike, is that fans will be good with a 6 win season. Buckle up for this one. The Sons then spin the random wheel to pick their defensive team from the current UCF players. In particular, the Sons have a hard time understanding the secondary and who will be a key player this season. Also, TMB and Josh Celiscar, who needs a bigger season? cow of the week talks Grothe and swamp ass, which are really the same thing when you think about it. Learn more about your ad choices. Visit megaphone.fm/adchoices